{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T08:26:16Z","timestamp":1773995176671,"version":"3.50.1"},"reference-count":175,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background\/Objectives: Congenital anomalies of the kidney and urinary tract (CAKUTs) represent the leading cause of pediatric chronic kidney disease, yet the molecular mechanisms underlying these malformations remain incompletely understood. While genetic studies have identified numerous CAKUT-associated genes, conventional knockout approaches often result in embryonic lethality or fail to reveal tissue-specific gene functions. This review aims to synthesize findings from conditional knockout mouse studies that have elucidated the spatiotemporal requirements of key signaling pathways during kidney development. Methods: We conducted a narrative synthesis of studies employing Cre-loxP conditional gene targeting in mouse models, identified through systematic searches of PubMed and cross-referencing of key primary research. Studies were selected based on their use of lineage-specific Cre drivers (Six2-Cre, Hoxb7-Cre, Foxd1-Cre) to investigate nephron progenitor maintenance, ureteric bud branching morphogenesis, and stromal\u2013epithelial interactions. Results: Conditional knockout studies have redefined CAKUT pathogenesis as a disorder of dose-dependent signaling, temporal regulation, and inter-compartmental communication. WNT\/\u03b2-catenin signaling operates in a biphasic, dose-dependent manner in nephron progenitors, with Six2-Cre-mediated \u03b2-catenin deletion causing premature progenitor depletion. BMP and FGF pathways demonstrate dose-dependent and context-specific functions in progenitor maintenance, while GDNF\/RET signaling is essential for ureteric bud outgrowth and branching. Importantly, stromal-specific deletions have uncovered non-cell-autonomous mechanisms regulating nephron formation. Haploinsufficiency studies demonstrate that partial pathway disruption can reduce nephron endowment without overt CAKUT, predisposing to adult-onset hypertension and chronic kidney disease. Conclusions: Conditional gene targeting has mechanistically redefined CAKUT from a collection of structural malformations to a spectrum of disorders arising from quantitative perturbations in lineage-specific signaling networks. These findings establish that phenotypic severity is determined by the degree of pathway disruption, the developmental timing of insult, and the compartment affected, providing a framework for interpreting oligogenic interactions and variable penetrance in human CAKUTs.<\/jats:p>","DOI":"10.3390\/biom16030458","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T10:11:12Z","timestamp":1773828672000},"page":"458","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dose-Dependent and Non-Autonomous Signaling in CAKUT: A Lineage-Specific Framework from Conditional Knockout Studies"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6529-5474","authenticated-orcid":false,"given":"Nela","family":"Kelam","sequence":"first","affiliation":[{"name":"Laboratory for Early Human Development, Department of Anatomy, Histology and Embryology, University of Split School of Medicine, \u0160oltanska 2A, 21000 Split, Croatia"},{"name":"Center for Translational Research in Biomedicine, University of Split School of Medicine, \u0160oltanska 2A, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6953-0135","authenticated-orcid":false,"given":"Petar","family":"Todorovi\u0107","sequence":"additional","affiliation":[{"name":"Laboratory for Early Human Development, Department of Anatomy, Histology and Embryology, University of Split School of Medicine, \u0160oltanska 2A, 21000 Split, Croatia"},{"name":"Center for Translational Research in Biomedicine, University of Split School of Medicine, \u0160oltanska 2A, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricija","family":"Bajt","sequence":"additional","affiliation":[{"name":"Laboratory for Early Human Development, Department of Anatomy, Histology and Embryology, University of Split School of Medicine, \u0160oltanska 2A, 21000 Split, Croatia"},{"name":"Center for Translational Research in Biomedicine, University of Split School of Medicine, \u0160oltanska 2A, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3452-389X","authenticated-orcid":false,"given":"Nikola","family":"Pavlovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, University of Split School of Medicine, 21000 Split, Croatia"},{"name":"Laboratory for Cardiometabolic Research, University of Split School of Medicine, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomislav","family":"Raki\u0107","sequence":"additional","affiliation":[{"name":"Laboratory for Early Human Development, Department of Anatomy, Histology and Embryology, University of Split School of Medicine, \u0160oltanska 2A, 21000 Split, Croatia"},{"name":"Center for Translational Research in Biomedicine, University of Split School of Medicine, \u0160oltanska 2A, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2182-2890","authenticated-orcid":false,"given":"Katarina","family":"Vukojevi\u0107","sequence":"additional","affiliation":[{"name":"Laboratory for Early Human Development, Department of Anatomy, Histology and Embryology, University of Split School of Medicine, \u0160oltanska 2A, 21000 Split, Croatia"},{"name":"Center for Translational Research in Biomedicine, University of Split School of Medicine, \u0160oltanska 2A, 21000 Split, Croatia"},{"name":"Mediterranean Institute for Life Sciences (MedILS), University of Split, Me\u0161trovi\u0107evo \u0160etali\u0161te 45, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Racetin","sequence":"additional","affiliation":[{"name":"Laboratory for Early Human Development, Department of Anatomy, Histology and Embryology, University of Split School of Medicine, \u0160oltanska 2A, 21000 Split, Croatia"},{"name":"Center for Translational Research in Biomedicine, University of Split School of Medicine, \u0160oltanska 2A, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"ref_1","unstructured":"Rehman, S., and Ahmed, D. (2025). Embryology, Kidney, Bladder, and Ureter. StatPearls, Ineligible Companies."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1038\/nrneph.2015.140","article-title":"Genetic, environmental, and epigenetic factors involved in CAKUT","volume":"11","author":"Nicolaou","year":"2015","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.semcdb.2018.08.013","article-title":"Impact of next generation sequencing on our understanding of CAKUT","volume":"91","author":"Nigam","year":"2019","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Capone, V.P., Morello, W., Taroni, F., and Montini, G. (2017). Genetics of Congenital Anomalies of the Kidney and Urinary Tract: The Current State of Play. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18040796"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s40348-021-00112-0","article-title":"Molecular causes of congenital anomalies of the kidney and urinary tract (CAKUT)","volume":"8","author":"Kohl","year":"2021","journal-title":"Mol. Cell. Pediatr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1007\/s00467-013-2684-4","article-title":"Single-gene causes of congenital anomalies of the kidney and urinary tract (CAKUT) in humans","volume":"29","author":"Vivante","year":"2014","journal-title":"Pediatr. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.bbi.2008.09.001","article-title":"Cautionary insights on knockout mouse studies: The gene or not the gene?","volume":"23","author":"Lawrence","year":"2009","journal-title":"Brain Behav. Immun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2883","DOI":"10.1038\/s41467-019-10748-2","article-title":"Generating viable mice with heritable embryonically lethal mutations using the CRISPR-Cas9 system in two-cell embryos","volume":"10","author":"Wu","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s10162-012-0324-5","article-title":"Conditional gene expression in the mouse inner ear using Cre-loxP","volume":"13","author":"Cox","year":"2012","journal-title":"J. Assoc. Res. Otolaryngol. JARO"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1038\/s41467-021-21427-6","article-title":"Cre-Controlled CRISPR mutagenesis provides fast and easy conditional gene inactivation in zebrafish","volume":"12","author":"Hans","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1177\/096368970000900607","article-title":"The Cre-loxP system: A versatile tool for targeting genes in a cell- and stage-specific manner","volume":"9","author":"Ray","year":"2000","journal-title":"Cell Transplant."},{"key":"ref_12","first-page":"F651","article-title":"The Cre\/loxP system and gene targeting in the kidney","volume":"276","author":"Stricklett","year":"1999","journal-title":"Am. J. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/s41581-022-00598-5","article-title":"Principles of human and mouse nephron development","volume":"18","author":"Schnell","year":"2022","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2912","DOI":"10.1016\/j.devcel.2024.07.013","article-title":"Comparative single-cell analyses identify shared and divergent features of human and mouse kidney development","volume":"59","author":"Kim","year":"2024","journal-title":"Dev. Cell"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Hochane, M., van den Berg, P.R., Fan, X., B\u00e9renger-Currias, N., Adegeest, E., Bialecka, M., Nieveen, M., Menschaart, M., Chuva de Sousa Lopes, S.M., and Semrau, S. (2019). Single-cell transcriptomics reveals gene expression dynamics of human fetal kidney development. PLoS Biol., 17.","DOI":"10.1371\/journal.pbio.3000152"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.stem.2008.05.020","article-title":"Six2 defines and regulates a multipotent self-renewing nephron progenitor population throughout mammalian kidney development","volume":"3","author":"Kobayashi","year":"2008","journal-title":"Cell Stem Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1159\/000531770","article-title":"Prioritization of Monogenic Congenital Anomalies of the Kidney and Urinary Tract Candidate Genes with Existing Single-Cell Transcriptomics Data of the Human Fetal Kidney","volume":"147","author":"Schierbaum","year":"2023","journal-title":"Nephron"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1242\/dev.057646","article-title":"Canonical Wnt9b signaling balances progenitor cell expansion and differentiation during kidney development","volume":"138","author":"Karner","year":"2011","journal-title":"Development"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3557","DOI":"10.1242\/dev.036335","article-title":"BMP7 promotes proliferation of nephron progenitor cells via a JNK-dependent mechanism","volume":"136","author":"Blank","year":"2009","journal-title":"Development"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"252","DOI":"10.4161\/org.6.4.12680","article-title":"GDNF\/Ret signaling and renal branching morphogenesis: From mesenchymal signals to epithelial cell behaviors","volume":"6","author":"Costantini","year":"2010","journal-title":"Organogenesis"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.stemcr.2014.08.008","article-title":"Identification of a multipotent self-renewing stromal progenitor population during mammalian kidney organogenesis","volume":"3","author":"Kobayashi","year":"2014","journal-title":"Stem Cell Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1002\/path.6195","article-title":"Hedgehog signalling in Foxd1 + embryonic kidney stromal progenitors controls nephron formation via Cxcl12 and Wnt5a","volume":"261","author":"Kim","year":"2023","journal-title":"J. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5937","DOI":"10.1038\/s41467-024-50171-w","article-title":"Single-cell multiomics reveals ENL mutation perturbs kidney developmental trajectory by rewiring gene regulatory landscape","volume":"15","author":"Song","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.devcel.2012.07.008","article-title":"Six2 and Wnt regulate self-renewal and commitment of nephron progenitors through shared gene regulatory networks","volume":"23","author":"Park","year":"2012","journal-title":"Dev. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"dev202279","DOI":"10.1242\/dev.202279","article-title":"Dose-dependent responses to canonical Wnt transcriptional complexes in the regulation of mammalian nephron progenitors","volume":"151","author":"Bugacov","year":"2024","journal-title":"Development"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1242\/dev.02861","article-title":"Reduction of BMP4 activity by gremlin 1 enables ureteric bud outgrowth and GDNF\/WNT11 feedback signalling during kidney branching morphogenesis","volume":"134","author":"Michos","year":"2007","journal-title":"Development"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3401","DOI":"10.1242\/dev.01251","article-title":"Gremlin-mediated BMP antagonism induces the epithelial-mesenchymal feedback signaling controlling metanephric kidney and limb organogenesis","volume":"131","author":"Michos","year":"2004","journal-title":"Development"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1007\/s00467-013-2589-2","article-title":"Bone morphogenetic protein signaling in nephron progenitor cells","volume":"29","author":"Oxburgh","year":"2014","journal-title":"Pediatr. Nephrol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Michos, O., Cebrian, C., Hyink, D., Grieshammer, U., Williams, L., D\u2019Agati, V., Licht, J.D., Martin, G.R., and Costantini, F. (2010). Kidney development in the absence of Gdnf and Spry1 requires Fgf10. PLoS Genet., 6.","DOI":"10.1371\/journal.pgen.1000809"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3859","DOI":"10.1242\/dev.01945","article-title":"Inactivation of FGF8 in early mesoderm reveals an essential role in kidney development","volume":"132","author":"Perantoni","year":"2005","journal-title":"Development"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1242\/dev.006155","article-title":"Wnt\/beta-catenin signaling regulates nephron induction during mouse kidney development","volume":"134","author":"Park","year":"2007","journal-title":"Development"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ydbio.2008.02.010","article-title":"Canonical WNT\/beta-catenin signaling is required for ureteric branching","volume":"317","author":"Bridgewater","year":"2008","journal-title":"Dev. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.ydbio.2007.11.016","article-title":"Beta-catenin is necessary to keep cells of ureteric bud\/Wolffian duct epithelium in a precursor state","volume":"314","author":"Marose","year":"2008","journal-title":"Dev. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Boivin, F.J., Sarin, S., Lim, J., Javidan, A., Svajger, B., Khalili, H., and Bridgewater, D. (2015). Stromally expressed \u03b2-catenin modulates Wnt9b signaling in the ureteric epithelium. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120347"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4640","DOI":"10.1073\/pnas.1213971110","article-title":"Role for compartmentalization in nephron progenitor differentiation","volume":"110","author":"Brown","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/j.devcel.2012.04.018","article-title":"FGF9 and FGF20 maintain the stemness of nephron progenitors in mice and man","volume":"22","author":"Barak","year":"2012","journal-title":"Dev. Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/367380a0","article-title":"Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret","volume":"367","author":"Schuchardt","year":"1994","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1242\/dev.122.6.1919","article-title":"Renal agenesis and hypodysplasia in ret-k- mutant mice result from defects in ureteric bud development","volume":"122","author":"Schuchardt","year":"1996","journal-title":"Development"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.semnephrol.2009.03.009","article-title":"Cell and molecular biology of kidney development","volume":"29","author":"Reidy","year":"2009","journal-title":"Semin. Nephrol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.diff.2016.01.007","article-title":"Modeling renal progenitors\u2014Defining the niche","volume":"91","author":"Tanigawa","year":"2016","journal-title":"Differentiation"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"dev159947","DOI":"10.1242\/dev.159947","article-title":"Hedgehog-GLI signaling in Foxd1-positive stromal cells promotes murine nephrogenesis via TGF\u03b2 signaling","volume":"145","author":"Rowan","year":"2018","journal-title":"Development"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/s41581-023-00742-9","article-title":"The genetics and pathogenesis of CAKUT","volume":"19","author":"Kolvenbach","year":"2023","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1681\/ASN.2017050561","article-title":"Novel Insights into the Pathogenesis of Monogenic Congenital Anomalies of the Kidney and Urinary Tract","volume":"29","author":"Vivante","year":"2018","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1038\/ng.476","article-title":"Etv4 and Etv5 are required downstream of GDNF and Ret for kidney branching morphogenesis","volume":"41","author":"Lu","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1681\/ASN.2017121265","article-title":"Whole-Exome Sequencing Identifies Causative Mutations in Families with Congenital Anomalies of the Kidney and Urinary Tract","volume":"29","author":"Connaughton","year":"2018","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1002\/ajmg.c.32006","article-title":"Disease mechanisms of monogenic congenital anomalies of the kidney and urinary tract American Journal of Medical Genetics Part C","volume":"190","author":"Connaughton","year":"2022","journal-title":"Am. J. Med. Genet. Part C Semin. Med. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/j.stem.2024.04.002","article-title":"Long-term expandable mouse and human-induced nephron progenitor cells enable kidney organoid maturation and modeling of plasticity and disease","volume":"31","author":"Huang","year":"2024","journal-title":"Cell Stem Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"7290","DOI":"10.1038\/s41467-025-62319-3","article-title":"Exome analysis links kidney malformations to developmental disorders and reveals causal genes","volume":"16","author":"Vena","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"101432","DOI":"10.1016\/j.gim.2025.101432","article-title":"Trio exome sequencing identifies de novo variants in novel candidate genes in 19.62% of CAKUT families","volume":"27","author":"Merz","year":"2025","journal-title":"Genet. Med."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Chambers, B.E., Weaver, N.E., and Wingert, R.A. (2023). The \u201c3Ds\u201d of Growing Kidney Organoids: Advances in Nephron Development, Disease Modeling, and Drug Screening. Cells, 12.","DOI":"10.3390\/cells12040549"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Liang, S., Wang, Y., Kang, M., Deng, J., Chen, L., Hong, X., Hou, F.F., and Zhang, F. (2023). Generation and characterization of an inducible renal proximal tubule-specific CreERT2 mouse. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1171637"},{"key":"ref_52","unstructured":"Skorecki, K., Chertow, G.M., Marsden, P.A., Taal, M.W., Yu, A.S.L., and Wasser, W.G. (2016). Brenner & Rector\u2019s the Kidney, Elsevier. [10th ed.]."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Maezawa, Y., Binnie, M., Li, C., Thorner, P., Hui, C.C., Alman, B., Taketo, M.M., and Quaggin, S.E. (2012). A new Cre driver mouse line, Tcf21\/Pod1-Cre, targets metanephric mesenchyme. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040547"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.kint.2017.09.015","article-title":"Haploinsufficiency for the Six2 gene increases nephron progenitor proliferation promoting branching and nephron number","volume":"93","author":"Combes","year":"2018","journal-title":"Kidney Int."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/(SICI)1520-6408(1999)24:3\/4<241::AID-DVG7>3.0.CO;2-R","article-title":"Expression of green fluorescent protein in the ureteric bud of transgenic mice: A new tool for the analysis of ureteric bud morphogenesis","volume":"24","author":"Srinivas","year":"1999","journal-title":"Dev. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1002\/dvg.20452","article-title":"A transgenic mouse that reveals cell shape and arrangement during ureteric bud branching","volume":"47","author":"Chi","year":"2009","journal-title":"Genesis"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"F249","DOI":"10.1152\/ajprenal.00313.2013","article-title":"RBP-J in FOXD1+ renal stromal progenitors is crucial for the proper development and assembly of the kidney vasculature and glomerular mesangial cells","volume":"306","author":"Lin","year":"2014","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Hum, S., Rymer, C., Schaefer, C., Bushnell, D., and Sims-Lucas, S. (2014). Ablation of the renal stroma defines its critical role in nephron progenitor and vasculature patterning. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0088400"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"F486","DOI":"10.1152\/ajprenal.00188.2006","article-title":"Novel mouse strain with Cre recombinase in 11beta-hydroxysteroid dehydrogenase-2-expressing cells","volume":"292","year":"2007","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"C216","DOI":"10.1152\/ajpcell.1998.275.1.C216","article-title":"Expression of an AQP2 Cre recombinase transgene in kidney and male reproductive system of transgenic mice","volume":"275","author":"Nelson","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/ki.2008.659","article-title":"Inactivation of Pkd1 in principal cells causes a more severe cystic kidney disease than in intercalated cells","volume":"75","author":"Raphael","year":"2009","journal-title":"Kidney Int."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/ki.2008.569","article-title":"The V-ATPase B1-subunit promoter drives expression of Cre recombinase in intercalated cells of the kidney","volume":"75","author":"Miller","year":"2009","journal-title":"Kidney Int."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4593","DOI":"10.1242\/dev.01324","article-title":"TGFbeta superfamily signals are required for morphogenesis of the kidney mesenchyme progenitor population","volume":"131","author":"Oxburgh","year":"2004","journal-title":"Development"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1097\/01.ASN.0000016444.90348.50","article-title":"Epithelial-specific Cre\/lox recombination in the developing kidney and genitourinary tract","volume":"13","author":"Shao","year":"2002","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1097\/01.ASN.0000016443.50138.CD","article-title":"A minimal Ksp-cadherin promoter linked to a green fluorescent protein reporter gene exhibits tissue-specific expression in the developing kidney and genitourinary tract","volume":"13","author":"Shao","year":"2002","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.ydbio.2007.10.014","article-title":"Fate mapping using Cited1-CreERT2 mice demonstrates that the cap mesenchyme contains self-renewing progenitor cells and gives rise exclusively to nephronic epithelia","volume":"313","author":"Boyle","year":"2008","journal-title":"Dev. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"6309","DOI":"10.1523\/JNEUROSCI.22-15-06309.2002","article-title":"Cortical excitatory neurons and glia, but not GABAergic neurons, are produced in the Emx1-expressing lineage","volume":"22","author":"Gorski","year":"2002","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"85","DOI":"10.2353\/ajpath.2010.090517","article-title":"Fate tracing reveals the pericyte and not epithelial origin of myofibroblasts in kidney fibrosis","volume":"176","author":"Humphreys","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"11959","DOI":"10.1074\/jbc.272.18.11959","article-title":"A 346-base pair region of the mouse gamma-glutamyl transpeptidase type II promoter contains sufficient cis-acting elements for kidney-restricted expression in transgenic mice","volume":"272","author":"Sepulveda","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1681\/ASN.2012050528","article-title":"Islet1 deletion causes kidney agenesis and hydroureter resembling CAKUT","volume":"24","author":"Kaku","year":"2013","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1002\/(SICI)1526-968X(200002)26:2<118::AID-GENE5>3.0.CO;2-S","article-title":"HoxB6-Cre transgenic mice express Cre recombinase in extra-embryonic mesoderm, in lateral plate and limb mesoderm and at the midbrain\/hindbrain junction","volume":"26","author":"Lowe","year":"2000","journal-title":"Genesis"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5301","DOI":"10.1242\/dev.129.22.5301","article-title":"Sonic hedgehog regulates proliferation and differentiation of mesenchymal cells in the mouse metanephric kidney","volume":"129","author":"Yu","year":"2002","journal-title":"Development"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"F965","DOI":"10.1152\/ajprenal.00402.2003","article-title":"Increased blood pressure in transgenic mice expressing both human renin and angiotensinogen in the renal proximal tubule","volume":"286","author":"Lavoie","year":"2004","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1681\/ASN.2007101078","article-title":"GUDMAP: The genitourinary developmental molecular anatomy project","volume":"19","author":"McMahon","year":"2008","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.1681\/ASN.V11122306","article-title":"Evaluation of a new tool for exploring podocyte biology: Mouse Nphs1 5\u2032 flanking region drives LacZ expression in podocytes","volume":"11","author":"Moeller","year":"2000","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"F1027","DOI":"10.1152\/ajprenal.2000.279.6.F1027","article-title":"Identification and characterization of a glomerular-specific promoter from the human nephrin gene","volume":"279","author":"Wong","year":"2000","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1097\/01.ASN.0000015614.68893.0B","article-title":"Two gene fragments that direct podocyte-specific expression in transgenic mice","volume":"13","author":"Moeller","year":"2002","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1002\/dvg.20334","article-title":"A unique mouse strain expressing Cre recombinase for tissue-specific analysis of gene function in palate and kidney development","volume":"45","author":"Lan","year":"2007","journal-title":"Genesis"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/gene.20017","article-title":"Generation of Pax2-Cre mice by modification of a Pax2 bacterial artificial chromosome","volume":"38","author":"Ohyama","year":"2004","journal-title":"Genesis"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.ydbio.2005.02.002","article-title":"Insertion of Cre into the Pax3 locus creates a new allele of Splotch and identifies unexpected Pax3 derivatives","volume":"280","author":"Engleka","year":"2005","journal-title":"Dev. Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1002\/(SICI)1526-968X(200002)26:2<162::AID-GENE21>3.0.CO;2-R","article-title":"Neural crest expression of Cre recombinase directed by the proximal Pax3 promoter in transgenic mice","volume":"26","author":"Li","year":"2000","journal-title":"Genesis"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1038\/nm.1865","article-title":"An efficient and versatile system for acute and chronic modulation of renal tubular function in transgenic mice","volume":"14","author":"Schonig","year":"2008","journal-title":"Nat. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.cell.2005.10.034","article-title":"Ephrin-B2 controls cell motility and adhesion during blood-vessel-wall assembly","volume":"124","author":"Foo","year":"2006","journal-title":"Cell"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"F1400","DOI":"10.1152\/ajprenal.00624.2013","article-title":"Mesangial cell alphavbeta8-integrin regulates glomerular capillary integrity and repair","volume":"306","author":"Li","year":"2014","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2576","DOI":"10.1158\/0008-5472.CAN-05-3241","article-title":"Renal cyst development in mice with conditional inactivation of the von Hippel-Lindau tumor suppressor","volume":"66","author":"Rankin","year":"2006","journal-title":"Cancer Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2809","DOI":"10.1242\/dev.01858","article-title":"Distinct and sequential tissue-specific activities of the LIM-class homeobox gene Lim1 for tubular morphogenesis during kidney development","volume":"132","author":"Kobayashi","year":"2005","journal-title":"Development"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/S1534-5807(04)00134-0","article-title":"Renin cells are precursors for multiple cell types that switch to the renin phenotype when homeostasis is threatened","volume":"6","author":"Pentz","year":"2004","journal-title":"Dev. Cell"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.neuron.2009.11.003","article-title":"Molecular identification of rapidly adapting mechanoreceptors and their developmental dependence on ret signaling","volume":"64","author":"Luo","year":"2009","journal-title":"Neuron"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1002\/dvg.20603","article-title":"A mouse line expressing Sall1-driven inducible Cre recombinase in the kidney mesenchyme","volume":"48","author":"Inoue","year":"2010","journal-title":"Genesis"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1097\/01.ASN.0000133023.89251.01","article-title":"Specific Cre\/Lox recombination in the mouse proximal tubule","volume":"15","author":"Rubera","year":"2004","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1093\/hmg\/ddt518","article-title":"Arap3 is dysregulated in a mouse model of hypotrichosis-lymphedema-telangiectasia and regulates lymphatic vascular development","volume":"23","author":"Kartopawiro","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/978-1-61779-851-1_17","article-title":"Access and use of the GUDMAP database of genitourinary development","volume":"886","author":"Davies","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1242\/dev.063594","article-title":"The GUDMAP database--an online resource for genitourinary research","volume":"138","author":"Harding","year":"2011","journal-title":"Development"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1538\/expanim.63.45","article-title":"Generation and analysis of serine protease inhibitor kazal type 3-cre driver mice","volume":"63","author":"Sakata","year":"2014","journal-title":"Exp. Anim."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"F608","DOI":"10.1152\/ajprenal.00297.2001","article-title":"Isolation of mouse THP gene promoter and demonstration of its kidney-specific activity in transgenic mice","volume":"282","author":"Zhu","year":"2002","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1002\/dvg.20566","article-title":"Generation of an allele to inactivate Wnt4 gene function conditionally in the mouse","volume":"47","author":"Shan","year":"2009","journal-title":"Genesis"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"19302","DOI":"10.1038\/s41598-020-76328-3","article-title":"Renal developmental genes are differentially regulated after unilateral ureteral obstruction in neonatal and adult mice","volume":"10","author":"Kubik","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s11248-019-00177-8","article-title":"Tamoxifen-independent recombination of reporter genes limits lineage tracing and mosaic analysis using CreER(T2) lines","volume":"29","author":"Daubel","year":"2020","journal-title":"Transgenic Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1002\/dvg.20750","article-title":"Efficient inducible Cre-mediated recombination in Tcf21 cell lineages in the heart and kidney","volume":"49","author":"Acharya","year":"2011","journal-title":"Genesis"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/978-1-0716-0385-7_13","article-title":"Generating Beta-Cell-Specific Transgenic Mice Using the Cre-Lox System","volume":"2128","author":"Smith","year":"2020","journal-title":"Methods Mol. Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.tig.2017.12.008","article-title":"Detecting and Avoiding Problems When Using the Cre-lox System","volume":"34","author":"Song","year":"2018","journal-title":"Trends Genet. TIG"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/j.immuni.2018.05.002","article-title":"Conditional Gene-Targeting in Mice: Problems and Solutions","volume":"48","author":"Becher","year":"2018","journal-title":"Immunity"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1002\/jbmr.4415","article-title":"Sites of Cre-recombinase activity in mouse lines targeting skeletal cells","volume":"36","author":"Couasnay","year":"2021","journal-title":"J. Bone Miner. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"F873","DOI":"10.1152\/ajprenal.00428.2018","article-title":"The Cre\/lox system: Cre-ating unintended damage","volume":"316","author":"Gewin","year":"2019","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"5214","DOI":"10.1038\/sj.emboj.7601381","article-title":"Six2 is required for suppression of nephrogenesis and progenitor renewal in the developing kidney","volume":"25","author":"Self","year":"2006","journal-title":"EMBO J."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"3529","DOI":"10.1242\/dev.121.11.3529","article-title":"Lack of beta-catenin affects mouse development at gastrulation","volume":"121","author":"Haegel","year":"1995","journal-title":"Development"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1083\/jcb.148.3.567","article-title":"Requirement for beta-catenin in anterior-posterior axis formation in mice","volume":"148","author":"Huelsken","year":"2000","journal-title":"J. Cell Biol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1681\/ASN.2006111206","article-title":"Glycogen synthase kinase-3 inactivation and stabilization of beta-catenin induce nephron differentiation in isolated mouse and rat kidney mesenchymes","volume":"18","author":"Kuure","year":"2007","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/0092-8674(93)90515-R","article-title":"WT-1 is required for early kidney development","volume":"74","author":"Kreidberg","year":"1993","journal-title":"Cell"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.neo.2015.12.001","article-title":"Nephron Progenitor But Not Stromal Progenitor Cells Give Rise to Wilms Tumors in Mouse Models with \u03b2-Catenin Activation or Wt1 Ablation and Igf2 Upregulation","volume":"18","author":"Huang","year":"2016","journal-title":"Neoplasia"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"4444","DOI":"10.1038\/ncomms5444","article-title":"WT1 controls antagonistic FGF and BMP-pSMAD pathways in early renal progenitors","volume":"5","author":"Motamedi","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2584","DOI":"10.1681\/ASN.2013080896","article-title":"Sall1 maintains nephron progenitors and nascent nephrons by acting as both an activator and a repressor","volume":"25","author":"Kanda","year":"2014","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1242\/dev.095851","article-title":"Sall1 balances self-renewal and differentiation of renal progenitor cells","volume":"141","author":"Basta","year":"2014","journal-title":"Development"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"3407","DOI":"10.1007\/s00467-025-06878-z","article-title":"Clinical characteristics of patients with SALL1-related disorder","volume":"40","author":"Asagai","year":"2025","journal-title":"Pediatr. Nephrol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.diff.2022.12.001","article-title":"Fgf8 promotes survival of nephron progenitors by regulating BAX\/BAK-mediated apoptosis","volume":"130","author":"Anderson","year":"2023","journal-title":"Differentiation"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.ydbio.2005.12.034","article-title":"Role of fibroblast growth factor receptors 1 and 2 in the metanephric mesenchyme","volume":"291","author":"Poladia","year":"2006","journal-title":"Dev. Biol."},{"key":"ref_117","first-page":"e04000","article-title":"Integrated \u03b2-catenin, BMP, PTEN, and Notch signalling patterns the nephron","volume":"3","author":"Lawrence","year":"2015","journal-title":"eLife"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.devcel.2005.05.016","article-title":"Wnt9b plays a central role in the regulation of mesenchymal to epithelial transitions underlying organogenesis of the mammalian urogenital system","volume":"9","author":"Carroll","year":"2005","journal-title":"Dev. Cell"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1681\/ASN.2020040478","article-title":"Biallelic Pathogenic GFRA1 Variants Cause Autosomal Recessive Bilateral Renal Agenesis","volume":"32","author":"Arora","year":"2021","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.ajhg.2007.10.008","article-title":"Renal aplasia in humans is associated with RET mutations","volume":"82","author":"Skinner","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1007\/s00439-012-1181-3","article-title":"Traditional and targeted exome sequencing reveals common, rare and novel functional deleterious variants in RET-signaling complex in a cohort of living US patients with urinary tract malformations","volume":"131","author":"Chatterjee","year":"2012","journal-title":"Hum. Genet."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/35019088","article-title":"GATA3 haplo-insufficiency causes human HDR syndrome","volume":"406","author":"Groenen","year":"2000","journal-title":"Nature"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Grote, D., Boualia, S.K., Souabni, A., Merkel, C., Chi, X., Costantini, F., Carroll, T., and Bouchard, M. (2008). Gata3 acts downstream of beta-catenin signaling to prevent ectopic metanephric kidney induction. PLoS Genet., 4.","DOI":"10.1371\/journal.pgen.1000316"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"dev189597","DOI":"10.1242\/dev.189597","article-title":"Stromal \u03b2-catenin activation impacts nephron progenitor differentiation in the developing kidney and may contribute to Wilms tumor","volume":"147","author":"Drake","year":"2020","journal-title":"Development"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Gon\u00e7alves, A., and Zeller, R. (2011). Genetic Analysis Reveals an Unexpected Role of BMP7 in Initiation of Ureteric Bud Outgrowth in Mouse Embryos. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019370"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.devcel.2014.10.015","article-title":"Eya1 interacts with Six2 and Myc to regulate expansion of the nephron progenitor pool during nephrogenesis","volume":"31","author":"Xu","year":"2014","journal-title":"Dev. Cell"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e41156","DOI":"10.7554\/eLife.41156","article-title":"Nephron progenitor commitment is a stochastic process influenced by cell migration","volume":"8","author":"Lawlor","year":"2019","journal-title":"eLife"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"3847","DOI":"10.1242\/dev.01944","article-title":"FGF8 is required for cell survival at distinct stages of nephrogenesis and for regulation of gene expression in nascent nephrons","volume":"132","author":"Grieshammer","year":"2005","journal-title":"Development"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/83792","article-title":"Vitamin A controls epithelial\/mesenchymal interactions through Ret expression","volume":"27","author":"Batourina","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1242\/dev.040287","article-title":"Non-cell-autonomous retinoid signaling is crucial for renal development","volume":"137","author":"Rosselot","year":"2010","journal-title":"Development"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1007\/s00467-024-06479-2","article-title":"Translational strategies to uncover the etiology of congenital anomalies of the kidney and urinary tract","volume":"40","author":"Vendrig","year":"2025","journal-title":"Pediatr. Nephrol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"177","DOI":"10.4161\/org.5.4.10048","article-title":"The many faces of RET dysfunction in kidney","volume":"5","author":"Jain","year":"2009","journal-title":"Organogenesis"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1101\/gad.1387206","article-title":"Critical and distinct roles for key RET tyrosine docking sites in renal development","volume":"20","author":"Jain","year":"2006","journal-title":"Genes Dev."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.devcel.2009.07.013","article-title":"Ret-dependent cell rearrangements in the Wolffian duct epithelium initiate ureteric bud morphogenesis","volume":"17","author":"Chi","year":"2009","journal-title":"Dev. Cell"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/bies.20357","article-title":"GDNF\/Ret signaling and the development of the kidney","volume":"28","author":"Costantini","year":"2006","journal-title":"Bioessays"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1034\/j.1399-0004.1999.560101.x","article-title":"Renal-coloboma syndrome: A multi-system developmental disorder caused by PAX2 mutations","volume":"56","author":"Eccles","year":"1999","journal-title":"Clin. Genet."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/ng0495-358","article-title":"Mutation of the PAX2 gene in a family with optic nerve colobomas, renal anomalies and vesicoureteral reflux","volume":"9","author":"Sanyanusin","year":"1995","journal-title":"Nat. Genet."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2958","DOI":"10.1101\/gad.240102","article-title":"Nephric lineage specification by Pax2 and Pax8","volume":"16","author":"Bouchard","year":"2002","journal-title":"Genes Dev."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1387\/ijdb.10535325","article-title":"Pax2 in development and renal disease","volume":"43","author":"Dressler","year":"1999","journal-title":"Int. J. Dev. Biol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1681\/ASN.2006070739","article-title":"Pax2 and pax8 regulate branching morphogenesis and nephron differentiation in the developing kidney","volume":"18","author":"Narlis","year":"2007","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/382076a0","article-title":"Renal and neuronal abnormalities in mice lacking GDNF","volume":"382","author":"Moore","year":"1996","journal-title":"Nature"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/j.ajhg.2012.10.007","article-title":"Copy-number disorders are a common cause of congenital kidney malformations","volume":"91","author":"Kiryluk","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1093\/ajh\/1.4.335","article-title":"Glomeruli and blood pressure. Less of one, more the other?","volume":"1","author":"Brenner","year":"1988","journal-title":"Am. J. Hypertens."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/0272-6386(95)90161-2","article-title":"Fewer nephrons at birth: A missing link in the etiology of essential hypertension?","volume":"26","author":"Mackenzie","year":"1995","journal-title":"Am. J. Kidney Dis."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1161\/01.HYP.0000050961.70182.56","article-title":"Nephron Number, Renal Function, and Arterial Pressure in Aged GDNF Heterozygous Mice","volume":"41","author":"Kett","year":"2003","journal-title":"Hypertension"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"128","DOI":"10.2215\/CJN.14661119","article-title":"Clinical Integration of Genome Diagnostics for Congenital Anomalies of the Kidney and Urinary Tract","volume":"16","author":"Westland","year":"2020","journal-title":"Clin. J. Am. Soc. Nephrol. CJASN"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1016\/j.ekir.2023.08.008","article-title":"Diagnostic Yield and Benefits of Whole Exome Sequencing in CAKUT Patients Diagnosed in the First Thousand Days of Life","volume":"8","author":"Werfel","year":"2023","journal-title":"Kidney Int. Rep."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"4001","DOI":"10.2147\/JIR.S506760","article-title":"Gene Editing: An Effective Tool for the Future Treatment of Kidney Disease","volume":"18","author":"Cao","year":"2025","journal-title":"J. Inflamm. Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1016\/j.kint.2020.04.045","article-title":"Human and mouse studies establish TBX6 in Mendelian CAKUT and as a potential driver of kidney defects associated with the 16p11.2 microdeletion syndrome","volume":"98","author":"Yang","year":"2020","journal-title":"Kidney Int."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"22434","DOI":"10.1038\/s41598-021-01790-6","article-title":"Single-cell RNA sequencing reveals differential cell cycle activity in key cell populations during nephrogenesis","volume":"11","author":"Bais","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"sfaf246","DOI":"10.1093\/ckj\/sfaf246","article-title":"CRISPR and gene editing for kidney diseases: Where are we?","volume":"18","author":"Huimei","year":"2025","journal-title":"Clin. Kidney J."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Liu, M., Cardilla, A., Ngeow, J., Gong, X., and Xia, Y. (2022). Studying Kidney Diseases Using Organoid Models. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.845401"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1038\/s41431-025-01929-3","article-title":"Clinical exome sequencing efficacy and phenotypic expansions involving non-isolated congenital anomalies of kidney and urinary tract (CAKUT+)","volume":"33","author":"Zhao","year":"2025","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Alobaidi, S. (2025). Emerging Biomarkers and Advanced Diagnostics in Chronic Kidney Disease: Early Detection Through Multi-Omics and AI. Diagnostics, 15.","DOI":"10.3390\/diagnostics15101225"},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Harris, M., Schuh, M.P., McKinney, D., Kaufman, K., and Erkan, E. (2022). Whole Exome Sequencing in a Population with Severe Congenital Anomalies of Kidney and Urinary Tract. Front. Pediatr., 10.","DOI":"10.3389\/fped.2022.898773"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"4903","DOI":"10.1038\/s41467-023-39740-7","article-title":"An integrated organoid omics map extends modeling potential of kidney disease","volume":"14","author":"Berthier","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Torabinavid, P., Khosropanah, M.H., Azimzadeh, A., and Kajbafzadeh, A.-M. (2025). Current strategies on kidney regeneration using tissue engineering approaches: A systematic review. BMC Nephrol., 26.","DOI":"10.1186\/s12882-025-03968-w"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"btad740","DOI":"10.1093\/bioinformatics\/btad740","article-title":"Artificial intelligence-assisted quantification and assessment of whole slide images for pediatric kidney disease diagnosis","volume":"40","author":"Feng","year":"2024","journal-title":"Bioinformatics"},{"key":"ref_159","first-page":"100767","article-title":"A high-definition spatiotemporal transcriptomic atlas of mammalian kidney development","volume":"6","author":"Jiang","year":"2025","journal-title":"Innovation"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.trsl.2012.01.020","article-title":"Genomic biomarkers for chronic kidney disease","volume":"159","author":"Ju","year":"2012","journal-title":"Transl. Res."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/s41598-020-80154-y","article-title":"Single cell RNA sequencing uncovers cellular developmental sequences and novel potential intercellular communications in embryonic kidney","volume":"11","author":"Matsui","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"9013","DOI":"10.1038\/s41598-024-59248-4","article-title":"Deep learning prediction of renal anomalies for prenatal ultrasound diagnosis","volume":"14","author":"Miguel","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"151584","DOI":"10.1016\/j.semnephrol.2025.151584","article-title":"Multi-Omics Integration in Nephrology: Advances, Challenges, and Future Directions","volume":"44","author":"Saliba","year":"2024","journal-title":"Semin. Nephrol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"7567","DOI":"10.1038\/s41467-025-62599-9","article-title":"Multimodal spatial transcriptomic characterization of mouse kidney injury and repair","volume":"16","author":"Xuanyuan","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Cross, B., Turner, R., and Pirmohamed, M. (2022). Polygenic risk scores: An overview from bench to bedside for personalised medicine. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.1000667"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"5302","DOI":"10.1038\/s41598-019-40457-1","article-title":"Development of the urogenital system is regulated via the 3\u2032UTR of GDNF","volume":"9","author":"Li","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"dev204964","DOI":"10.1242\/dev.204964","article-title":"Defects in nephrogenesis result in an expansion of the Foxd1+ stromal progenitor population","volume":"153","author":"Michalopulos","year":"2026","journal-title":"Development"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"5276","DOI":"10.1038\/s41467-021-25014-7","article-title":"Translating polygenic risk scores for clinical use by estimating the confidence bounds of risk prediction","volume":"12","author":"Sun","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.stem.2021.11.001","article-title":"Genome-wide screening in human kidney organoids identifies developmental and disease-related aspects of nephrogenesis","volume":"29","author":"Ungricht","year":"2022","journal-title":"Cell Stem Cell"},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Garreta, E., Moya-Rull, D., Centeno, A., Marco, A., Ullate-Agote, A., Amato, G., Aranda, C.J., Oria, R., Lozano-Ojalvo, D., and Pool, M.B.F. (2025). Systematic production of human kidney organoids for transplantation in porcine kidneys during ex vivo machine perfusion. Nat. Biomed. Eng.","DOI":"10.1038\/s41551-025-01542-1"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41536-020-0093-4","article-title":"Overcoming kidney organoid challenges for regenerative medicine","volume":"5","author":"Geuens","year":"2020","journal-title":"NPJ Regen. Med."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"e240174","DOI":"10.1530\/ERC-24-0174","article-title":"Biology of RET receptor and its ligands: Focus on the nervous system","volume":"32","author":"Mahato","year":"2025","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Nakanoh, H., Tsuji, K., Fukushima, K., Uchida, N., Haraguchi, S., Kitamura, S., and Wada, J. (2025). Kidney Organoids: Current Advances and Applications. Life, 15.","DOI":"10.1038\/s41598-025-26155-1"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.stem.2023.04.011","article-title":"Human pluripotent-stem-cell-derived organoids for drug discovery and evaluation","volume":"30","author":"Vandana","year":"2023","journal-title":"Cell Stem Cell"},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Fourikou, M., and Dotis, J. (2026). From Genes to Malformations: Molecular Mechanisms Driving the Pathogenesis of Congenital Anomalies of the Kidney and Urinary Tract. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27010017"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/3\/458\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T05:20:56Z","timestamp":1773984056000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/3\/458"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,18]]},"references-count":175,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["biom16030458"],"URL":"https:\/\/doi.org\/10.3390\/biom16030458","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,18]]}}}