{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:48:07Z","timestamp":1792086487070,"version":"4.4.0"},"reference-count":92,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The pancreas plays a crucial role in digestion and blood glucose regulation. Current animal models, primarily mice and zebrafish, have limited the exploration of pancreatic biology from an evolutionary-developmental perspective. Tetrapod vertebrate axolotl (<jats:italic>Ambystoma mexicanum<\/jats:italic>) serves as a valuable model in developmental, regenerative, and evolutionary biology. However, the fundamental biology of the axolotl pancreas remains underexplored. This study aims to characterize the unique developmental, functional, and evolutionary features of the axolotl pancreas to expand the understanding of pancreatic biology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted morphological, histological, and transcriptomic analyses to investigate the axolotl pancreas. Pancreatic development was observed using <jats:italic>in situ<\/jats:italic> hybridization and immunostaining for key pancreatic markers. RNA sequencing was performed to profile global gene expression during larva and adult stages. And differential gene expression analysis was used to characterize the conserved and unique gene patterns in the axolotl pancreas. Functional assays, including glucose tolerance tests and insulin tolerance tests, were optimized for individual axolotls. To assess pancreatic gene function, <jats:italic>Pdx1<\/jats:italic> mutants were generated using CRISPR\/Cas9-mediated gene editing, and their effects on pancreatic morphology, endocrine cell populations, and glucose homeostasis were analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The axolotl pancreas contains all known pancreatic cell types and develops from dorsal and ventral buds. Both of buds contribute to exocrine and endocrine glands. The dorsal bud produces the major endocrine cell types, while the ventral bud generates \u03b1 and \u03b4 cells, but not \u03b2 cells. Differential gene expression analysis indicated a transition in global gene expression from pancreatic cell fate commitment and the cell cycle to glucose response, hormone synthesis, and secretion, following the development progression. Notably, the adult axolotl pancreas exhibits slower metabolic activity compared to mammals, as evidenced by the results of GTT and ITT. The mutation of <jats:italic>Pdx1<\/jats:italic> resulted in hyperglycemia and a significant reduction in pancreatic cell mass, including a complete loss of endocrine cells, although it did not lead to a lethal phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This study examines the axolotl pancreas, highlighting the conservation of pancreatic development. Our study highlights the unique features of the axolotl pancreas and broadens the scope of animal models available for pancreatic evolution and disease research.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcell.2025.1531903","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T06:43:44Z","timestamp":1738305824000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Revealing the biological features of the axolotl pancreas as a new research model"],"prefix":"10.3389","volume":"13","author":[{"given":"Hui","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangcong","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binbin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiying","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxian","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weimin","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyu","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina","family":"St\u00fctzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jifeng","family":"Fei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,31]]},"reference":[{"key":"B1","first-page":"111","article-title":"A natural body window to study human pancreatic islet cell function and survival","volume":"1","author":"Abdulreda","year":"2013","journal-title":"replacement, Regen. & reprogramming"},{"key":"B2","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.cmet.2017.08.007","article-title":"Pancreatic \u03b2 cell regeneration as a possible therapy for diabetes","volume":"27","author":"Aguayo-Mazzucato","year":"2018","journal-title":"Cell Metab."},{"key":"B3","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1186\/s13287-020-01977-0","article-title":"NKX6.1 transcription factor: a crucial regulator of pancreatic \u03b2 cell development, identity, and proliferation","volume":"11","author":"Aigha","year":"2020","journal-title":"Stem Cell Res. & Ther."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1792","DOI":"10.2337\/db06-1513","article-title":"Glucose infusion in mice: a new model to induce beta-cell replication","volume":"56","author":"Alonso","year":"2007","journal-title":"Diabetes"},{"key":"B5","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/j.bbagen.2014.11.005","article-title":"Pancreatic polypeptide regulates glucagon release through PPYR1 receptors expressed in mouse and human alpha-cells","volume":"1850","author":"Arag\u00f3n","year":"2015","journal-title":"Biochimica Biophysica Acta (BBA) - General Subj."},{"key":"B6","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1053\/gast.2001.22158","article-title":"Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin","volume":"120","author":"Asakawa","year":"2001","journal-title":"Gastroenterology"},{"key":"B7","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1016\/j.cels.2016.08.011","article-title":"A single-cell transcriptomic map of the human and mouse pancreas reveals inter- and intra-cell population structure","volume":"3","author":"Baron","year":"2016","journal-title":"Cell Syst."},{"key":"B8","doi-asserted-by":"publisher","first-page":"100214","DOI":"10.1016\/j.xgen.2022.100214","article-title":"Type 1 diabetes risk genes mediate pancreatic beta cell survival in response to proinflammatory cytokines","volume":"2","author":"Benaglio","year":"2022","journal-title":"Cell Genom."},{"key":"B9","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/2041-9139-4-3","article-title":"Comparative pelvic development of the axolotl (Ambystoma mexicanum) and the Australian lungfish (Neoceratodus forsteri): conservation and innovation across the fish-tetrapod transition","volume":"4","author":"Boisvert","year":"2013","journal-title":"EvoDevo"},{"key":"B10","doi-asserted-by":"publisher","first-page":"49","DOI":"10.2337\/diab.38.1.49","article-title":"Compensatory growth of pancreatic beta-cells in adult rats after short-term glucose infusion","volume":"38","author":"Bonner-Weir","year":"1989","journal-title":"Diabetes."},{"key":"B11","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1369\/0022155415570969","article-title":"Human islet morphology revisited: human and rodent islets are not so different after all","volume":"63","author":"Bonner-Weir","year":"2015","journal-title":"J. Histochem Cytochem."},{"key":"B12","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1016\/j.celrep.2016.12.063","article-title":"A tissue-mapped axolotl de novo transcriptome enables identification of limb regeneration factors","volume":"18","author":"Bryant","year":"2017","journal-title":"Cell Rep."},{"key":"B13","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.ydbio.2008.01.011","article-title":"Pdx-1 and Ptf1a concurrently determine fate specification of pancreatic multipotent progenitor cells","volume":"316","author":"Burlison","year":"2008","journal-title":"Dev. Biol."},{"key":"B14","first-page":"79","article-title":"Functional and structural regeneration in the axolotl heart (Ambystoma mexicanum) after partial ventricular amputation","volume":"80","author":"Cano-Mart\u00ednez","year":"2010","journal-title":"Arch. Cardiol. Mex."},{"key":"B15","doi-asserted-by":"publisher","first-page":"382","DOI":"10.3390\/nu12020382","article-title":"Metabolic and cognitive effects of ranolazine in type 2 diabetes mellitus: data from an in vivo model","volume":"12","author":"Cassano","year":"2020","journal-title":"vivo model"},{"key":"B16","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1038\/s41581-020-0278-5","article-title":"Genetics of diabetes mellitus and diabetes complications","volume":"16","author":"Cole","year":"2020","journal-title":"Nat. Rev. Nephrol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e55665","DOI":"10.7554\/eLife.55665","article-title":"Spatiotemporal control of cell cycle acceleration during axolotl spinal cord regeneration","volume":"10","author":"Cura Costa","year":"2021","journal-title":"Elife."},{"key":"B18","doi-asserted-by":"publisher","first-page":"eadq0702","DOI":"10.1126\/sciadv.adq0702","article-title":"Single-cell profiling of the amphioxus digestive tract reveals conservation of endocrine cells in chordates","volume":"10","author":"Dai","year":"2024","journal-title":"Sci. Adv."},{"key":"B19","doi-asserted-by":"publisher","first-page":"E214","DOI":"10.1152\/ajpendo.1979.237.3.E214","article-title":"Glucose clamp technique: a method for quantifying insulin secretion and resistance","volume":"237","author":"DeFronzo","year":"1979","journal-title":"Am. J. Physiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"101248","DOI":"10.1016\/j.molmet.2021.101248","article-title":"Dysregulation of the Pdx1\/Ovol2\/Zeb2 axis in dedifferentiated \u03b2-cells triggers the induction of genes associated with epithelial-mesenchymal transition in diabetes","volume":"53","author":"de Jesus","year":"2021","journal-title":"Mol. Metab."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1993","DOI":"10.1126\/science.1077804","article-title":"Ectoderm to mesoderm lineage switching during axolotl tail regeneration","volume":"298","author":"Echeverri","year":"2002","journal-title":"Science"},{"key":"B22","doi-asserted-by":"publisher","first-page":"2908","DOI":"10.1038\/s41596-018-0071-0","article-title":"Application and optimization of CRISPR\u2013Cas9-mediated genome engineering in axolotl (Ambystoma mexicanum)","volume":"13","author":"Fei","year":"2018","journal-title":"Nat. Protoc."},{"key":"B23","doi-asserted-by":"publisher","first-page":"12501","DOI":"10.1073\/pnas.1706855114","article-title":"Efficient gene knockin in axolotl and its use to test the role of satellite cells in limb regeneration","volume":"114","author":"Fei","year":"2017","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.pan.2013.03.009","article-title":"Cdkn1a is a key mediator of rat pancreatic stellate cell senescence","volume":"13","author":"Fitzner","year":"2013","journal-title":"Pancreatology"},{"key":"B25","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1101\/gad.1360106","article-title":"Targeted deletion of a cis-regulatory region reveals differential gene dosage requirements for Pdx1 in foregut organ differentiation and pancreas formation","volume":"20","author":"Fujitani","year":"2006","journal-title":"Genes Dev."},{"key":"B26","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.cmet.2013.12.002","article-title":"Pdx1 maintains \u03b2 cell identity and function by repressing an \u03b1 cell program","volume":"19","author":"Gao","year":"2014","journal-title":"Cell Metab."},{"key":"B27","volume-title":"Beta-cell fate: from gene circuits to disease mechanisms","author":"Ghila","year":"2022"},{"key":"B28","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1139\/z97-161","article-title":"Fine structure and immunocytochemistry of cells within the endocrine pancreas of the gar (Lepisosteus osseus)","volume":"76","author":"Groff","year":"1998","journal-title":"Can. J. Zoology"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1038\/s41559-018-0673-5","article-title":"Shark genomes provide insights into elasmobranch evolution and the origin of vertebrates","volume":"2","author":"Hara","year":"2018","journal-title":"Nat. Ecol. & Evol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"3361","DOI":"10.1038\/s41596-020-0376-7","article-title":"Combined whole-mount fluorescence in situ hybridization and antibody staining in zebrafish embryos and larvae","volume":"15","author":"He","year":"2020","journal-title":"Nat. Protoc."},{"key":"B31","doi-asserted-by":"publisher","first-page":"2586","DOI":"10.2337\/diabetes.54.9.2586","article-title":"Conditional expression demonstrates the role of the homeodomain transcription factor Pdx1 in maintenance and regeneration of beta-cells in the adult pancreas","volume":"54","author":"Holland","year":"2005","journal-title":"Diabetes"},{"key":"B32","doi-asserted-by":"publisher","first-page":"e2004","DOI":"10.1002\/hsr2.2004","article-title":"Diabetes mellitus, the fastest growing global public health concern: early detection should be focused","volume":"7","author":"Hossain","year":"2024","journal-title":"Health Sci. Rep."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e10","DOI":"10.4081\/ejh.2009.e10","article-title":"Immunohistochemical localization of glucagon and pancreatic polypeptide on rat endocrine pancreas: coexistence in rat islet cells","volume":"53","author":"Huang","year":"2009","journal-title":"Eur. J. Histochem."},{"key":"B34","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1530\/eje.0.1460129","article-title":"Pancreas duodenum homeobox-1 regulates pancreas development during embryogenesis and islet cell function in adulthood","volume":"146","author":"Hui","year":"2002","journal-title":"Eur. J. Endocrinol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1002\/ar.21154","article-title":"The anatomy of the gastrointestinal tract of the African lungfish, Protopterus annectens","volume":"293","author":"Icardo","year":"2010","journal-title":"Protopterus annectens"},{"key":"B36","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1038\/371606a0","article-title":"Insulin-promoter-factor 1 is required for pancreas development in mice","volume":"371","author":"Jonsson","year":"1994","journal-title":"Nature."},{"key":"B37","article-title":"The lungfish endocrine system","volume-title":"The Biology of lungfishes","author":"Joss","year":"2010"},{"key":"B38","doi-asserted-by":"publisher","first-page":"102513","DOI":"10.1016\/j.scr.2021.102513","article-title":"Cdkn1a deletion or suppression by cyclic stretch enhance the osteogenic potential of bone marrow mesenchymal stem cell-derived cultures","volume":"56","author":"Juran","year":"2021","journal-title":"Stem Cell Res."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.3390\/ijms20071521","article-title":"Effects of motilin receptor agonists and ghrelin in human motilin receptor transgenic mice","volume":"20","author":"Kawamura","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/bs.mcb.2016.02.009","article-title":"Zebrafish pancreas as a model for development and disease","volume":"134","author":"Kimmel","year":"2016","journal-title":"Methods cell Biol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"278","DOI":"10.3389\/fendo.2019.00278","article-title":"Regulation of gastrointestinal motility by motilin and ghrelin in vertebrates","volume":"10","author":"Kitazawa","year":"2019","journal-title":"Front. Endocrinol. (Lausanne)."},{"key":"B42","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.peptides.2006.09.024","article-title":"A role for pancreatic polypeptide in feeding and body weight regulation","volume":"28","author":"Kojima","year":"2007","journal-title":"Peptides"},{"key":"B43","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1172\/JCI21845","article-title":"PDX-1 haploinsufficiency limits the compensatory islet hyperplasia that occurs in response to insulin resistance","volume":"114","author":"Kulkarni","year":"2004","journal-title":"J. Clin. Invest."},{"key":"B44","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1186\/s12915-020-00840-1","article-title":"Pancreatic and intestinal endocrine cells in zebrafish share common transcriptomic signatures and regulatory programmes","volume":"18","author":"Lavergne","year":"2020","journal-title":"BMC Biol."},{"key":"B45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/9781119876007.ch1","article-title":"Development of the pancreas and related structures","volume-title":"The pancreas: an integrated textbook of basic science, medicine, and surgery","author":"Lewis","year":"2023"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.3390\/biom11091300","article-title":"Progress in gene-editing technology of zebrafish","volume":"11","author":"Li","year":"2021","journal-title":"Biomolecules"},{"key":"B47","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1016\/j.ydbio.2004.02.023","article-title":"Differential requirement for ptf1a in endocrine and exocrine lineages of developing zebrafish pancreas","volume":"270","author":"Lin","year":"2004","journal-title":"Dev. Biol."},{"key":"B48","volume-title":"Anatomy and histology of the pancreas","author":"Longnecker","year":"2014"},{"key":"B49","doi-asserted-by":"publisher","first-page":"3449","DOI":"10.3390\/ani13223449","article-title":"Evolutionary insights into the relationship of frogs, salamanders, and caecilians and their adaptive traits, with an emphasis on salamander regeneration and longevity","volume":"13","author":"Lu","year":"2023","journal-title":"Animals"},{"key":"B50","doi-asserted-by":"publisher","first-page":"eabp9262","DOI":"10.1126\/science.abp9262","article-title":"Single-cell analyses of axolotl telencephalon organization, neurogenesis, and regeneration","volume":"377","author":"Lust","year":"2022","journal-title":"Science"},{"key":"B51","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1111\/dgd.12565","article-title":"Zebrafish as a model for studying functional pancreatic \u03b2 cells development and regeneration","volume":"60","author":"Matsuda","year":"2018","journal-title":"Dev. Growth Differ."},{"key":"B52","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1016\/j.molmed.2024.05.002","article-title":"Leveraging zebrafish to investigate pancreatic development, regeneration, and diabetes","volume":"30","author":"Mi","year":"2024","journal-title":"Trends Mol. Med."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1844","DOI":"10.2337\/db08-0628","article-title":"Regeneration of the pancreas in adult zebrafish","volume":"58","author":"Moss","year":"2009","journal-title":"Diabetes"},{"key":"B54","doi-asserted-by":"publisher","first-page":"2386","DOI":"10.1093\/molbev\/msq121","article-title":"Parallel retention of Pdx2 genes in cartilaginous fish and coelacanths","volume":"27","author":"Mulley","year":"2010","journal-title":"Mol. Biol. Evol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.cels.2016.09.002","article-title":"A single-cell transcriptome atlas of the human pancreas","volume":"3","author":"Muraro","year":"2016","journal-title":"Cell Syst."},{"key":"B56","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1242\/dev.122.3.983","article-title":"PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum","volume":"122","author":"Offield","year":"1996","journal-title":"Development"},{"key":"B57","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1172\/JCI37028","article-title":"The diabetes gene Pdx1 regulates the transcriptional network of pancreatic endocrine progenitor cells in mice","volume":"119","author":"Oliver-Krasinski","year":"2009","journal-title":"J. Clin. Invest."},{"key":"B58","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1002\/dvdy.22584","article-title":"Pancreas organogenesis: from bud to plexus to gland","volume":"240","author":"Pan","year":"2011","journal-title":"Dev. Dyn."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1638","DOI":"10.1136\/gut.2004.062604","article-title":"Ghrelin: a new player in the control of gastrointestinal functions","volume":"54","author":"Peeters","year":"2005","journal-title":"Gut."},{"key":"B60","doi-asserted-by":"publisher","first-page":"4458","DOI":"10.1038\/s41467-021-24788-0","article-title":"Pancreatic Ppy-expressing \u03b3-cells display mixed phenotypic traits and the adaptive plasticity to engage insulin production","volume":"12","author":"Perez-Frances","year":"2021","journal-title":"Nat. Commun."},{"key":"B61","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/j.ebiom.2019.03.021","article-title":"Arid1a regulates insulin sensitivity and lipid metabolism","volume":"42","author":"Qu","year":"2019","journal-title":"EBioMedicine"},{"key":"B62","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.2337\/db08-1198","article-title":"Adaptive beta-cell proliferation is severely restricted with advanced age","volume":"58","author":"Rankin","year":"2009","journal-title":"Diabetes"},{"key":"B63","doi-asserted-by":"publisher","first-page":"e219","DOI":"10.1038\/emm.2016.6","article-title":"Pancreatic regulation of glucose homeostasis","volume":"48","author":"R\u00f6der","year":"2016","journal-title":"Exp. & Mol. Med."},{"key":"B64","doi-asserted-by":"publisher","first-page":"2575","DOI":"10.2337\/dbi20-0039","article-title":"There is something about insulin granules","volume":"69","author":"Roep","year":"2020","journal-title":"Diabetes"},{"key":"B65","doi-asserted-by":"publisher","first-page":"bvab128","DOI":"10.1210\/jendso\/bvab128","article-title":"Revisiting regulators of human \u03b2-cell mass to achieve \u03b2-cell-centric approach toward type 2 diabetes","volume":"5","author":"Sasaki","year":"2021","journal-title":"J. Endocr. Soc."},{"key":"B66","doi-asserted-by":"publisher","first-page":"e2017176118","DOI":"10.1073\/pnas.2017176118","article-title":"The giant axolotl genome uncovers the evolution, scaling, and transcriptional control of complex gene loci","volume":"118","author":"Schloissnig","year":"2021","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B67","doi-asserted-by":"publisher","first-page":"4398","DOI":"10.1210\/jc.2003-030046","article-title":"Agenesis of human pancreas due to decreased half-life of insulin promoter factor 1","volume":"88","author":"Schwitzgebel","year":"2003","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B68","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1007\/s11154-019-09504-0","article-title":"Can blood glucose value really be referred to as a metabolic parameter?","volume":"20","author":"Simon","year":"2019","journal-title":"Rev. Endocr. Metabolic Disord."},{"key":"B69","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1242\/dev.121.6.1569","article-title":"Developmental biology of the pancreas","volume":"121","author":"Slack","year":"1995","journal-title":"Development"},{"key":"B70","doi-asserted-by":"publisher","first-page":"101440","DOI":"10.1016\/j.molmet.2022.101440","article-title":"Comparative analysis of oral and intraperitoneal glucose tolerance tests in mice","volume":"57","author":"Small","year":"2022","journal-title":"Mol. Metab."},{"key":"B71","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1101\/gr.241901.118","article-title":"A chromosome-scale assembly of the axolotl genome","volume":"29","author":"Smith","year":"2019","journal-title":"Genome Res."},{"key":"B72","doi-asserted-by":"crossref","DOI":"10.1096\/fasebj.2022.36.S1.R1914","article-title":"A novel animal model in diabetes: regeneration of \u03b2 cells in the axolotl salamander? 36","author":"S\u00f8rensen","year":"2022"},{"key":"B73","doi-asserted-by":"publisher","first-page":"135","DOI":"10.4161\/isl.2.3.11815","article-title":"Pancreatic islet plasticity: interspecies comparison of islet architecture and composition","volume":"2","author":"Steiner","year":"2010","journal-title":"Islets."},{"key":"B74","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1038\/ng0197-106","article-title":"Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence","volume":"15","author":"Stoffers","year":"1997","journal-title":"Nat. Genet."},{"key":"B75","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/1741-7007-10-103","article-title":"Lens regeneration in axolotl: new evidence of developmental plasticity","volume":"10","author":"Suetsugu-Maki","year":"2012","journal-title":"BMC Biol."},{"key":"B76","doi-asserted-by":"crossref","DOI":"10.1016\/B0-12-386860-2\/00212-4","article-title":"Endocrine pancreas","volume-title":"Encyclopedia of gastroenterology","author":"Susan","year":"2004"},{"key":"B77","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1093\/af\/vfz020","article-title":"The use of zebrafish (Danio rerio) as biomedical models","volume":"9","author":"Teame","year":"2019","journal-title":"Anim. Front."},{"key":"B78","doi-asserted-by":"publisher","first-page":"2557","DOI":"10.2337\/diabetes.54.9.2557","article-title":"Very slow turnover of beta-cells in aged adult mice","volume":"54","author":"Teta","year":"2005","journal-title":"Diabetes"},{"key":"B79","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1056\/nejm197108192850806","article-title":"Glucagon physiology and pathophysiology","volume":"285","author":"Unger","year":"1971","journal-title":"N. Engl. J. Med."},{"key":"B80","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1203\/PDR.0b013e318186e609","article-title":"Zebrafish as a developmental model organism for pediatric research","volume":"64","author":"Veldman","year":"2008","journal-title":"Pediatr. Res."},{"key":"B81","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1159\/000504294","article-title":"Advancements to the axolotl model for regeneration and aging","volume":"66","author":"Vieira","year":"2020","journal-title":"Gerontology"},{"key":"B82","doi-asserted-by":"publisher","first-page":"11900","DOI":"10.3389\/ti.2024.11900","article-title":"Glucose concentration in regulating induced pluripotent stem cells differentiation toward insulin-producing cells","volume":"37","author":"Wang","year":"2024","journal-title":"Cells"},{"key":"B83","doi-asserted-by":"publisher","first-page":"2091615","DOI":"10.1155\/2022\/2091615","article-title":"Cebpb regulates skeletal stem cell osteogenic differentiation and fracture healing via the WNT\/\u03b2-Catenin pathway","volume":"2022","author":"Wang","year":"2022","journal-title":"Stem Cells Int."},{"key":"B84","doi-asserted-by":"publisher","first-page":"eabp9444","DOI":"10.1126\/science.abp9444","article-title":"Single-cell Stereo-seq reveals induced progenitor cells involved in axolotl brain regeneration","volume":"377","author":"Wei","year":"2022","journal-title":"Science"},{"key":"B85","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.3390\/jcm8091369","article-title":"The use of genetically engineered mouse models for studying the function of mutated driver genes in pancreatic cancer","volume":"8","author":"Weng","year":"2019","journal-title":"J. Clin. Med."},{"key":"B86","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.ygcen.2004.02.017","article-title":"Tilapia islet grafts are highly alloxan-resistant","volume":"137","author":"Xu","year":"2004","journal-title":"Gen. Comp. Endocrinol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s13619-020-00052-6","article-title":"In vivo generation and regeneration of \u03b2 cells in zebrafish","volume":"9","author":"Yang","year":"2020","journal-title":"Cell Regen."},{"key":"B92","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.xpro.2021.100728","article-title":"Ontogenetic and phylogenetic development of the endocrine pancreas (islet organ) in fishes","volume":"116","author":"Youson","year":"1999","journal-title":"Gen. Comp. Endocrinol."},{"key":"B88","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1038\/s41422-021-00486-w","article-title":"Sequential progenitor states mark the generation of pancreatic endocrine lineages in mice and humans","volume":"31","author":"Yu","year":"2021","journal-title":"Cell Res."},{"key":"B89","doi-asserted-by":"publisher","first-page":"dev179051","DOI":"10.1242\/dev.179051","article-title":"Understanding generation and regeneration of pancreatic \u03b2 cells from a single-cell perspective","volume":"147","author":"Yu","year":"2020","journal-title":"Development."},{"key":"B90","doi-asserted-by":"publisher","first-page":"903","DOI":"10.2337\/db20-0599","article-title":"Cell cycle regulation of the Pdx1 transcription factor in developing pancreas and insulin-producing \u03b2-cells","volume":"70","author":"Zhu","year":"","journal-title":"Diabetes."},{"key":"B91","doi-asserted-by":"publisher","first-page":"100728","DOI":"10.1016\/j.xpro.2021.100728","article-title":"Protocol for in vivo and ex vivo assessments of glucose-stimulated insulin secretion in mouse islet \u03b2 cells","volume":"2","author":"Zhu","year":"","journal-title":"Star. Protoc."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2025.1531903\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T06:43:53Z","timestamp":1738305833000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2025.1531903\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,31]]},"references-count":92,"alternative-id":["10.3389\/fcell.2025.1531903"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2025.1531903","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,31]]},"article-number":"1531903"}}