{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T22:08:52Z","timestamp":1770329332987,"version":"3.49.0"},"reference-count":76,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T00:00:00Z","timestamp":1629072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["17SDG33G70982"],"award-info":[{"award-number":["17SDG33G70982"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Endocytic trafficking is an under-appreciated pathway in cardiac development. Several genes related to endocytic trafficking have been uncovered in a mutagenic ENU screen, in which mutations led to congenital heart defects (CHDs). In this article, we review the relationship between these genes (including LRP1 and LRP2) and cardiac neural crest cells (CNCCs) during cardiac development. Mice with an ENU-induced Lrp1 mutation exhibit a spectrum of CHDs. Conditional deletion using a floxed Lrp1 allele with different Cre drivers showed that targeting neural crest cells with Wnt1-Cre expression replicated the full cardiac phenotypes of the ENU-induced Lrp1 mutation. In addition, LRP1 function in CNCCs is required for normal OFT lengthening and survival\/expansion of the cushion mesenchyme, with other cell lineages along the NCC migratory path playing an additional role. Mice with an ENU-induced and targeted Lrp2 mutation demonstrated the cardiac phenotype of common arterial trunk (CAT). Although there is no impact on CNCCs in Lrp2 mutants, the loss of LRP2 results in the depletion of sonic hedgehog (SHH)-dependent cells in the second heart field. SHH is known to be crucial for CNCC survival and proliferation, which suggests LRP2 has a non-autonomous role in CNCCs. In this article, other endocytic trafficking proteins that are associated with CHDs that may play roles in the NCC pathway during development, such as AP1B1, AP2B1, FUZ, MYH10, and HECTD1, are reviewed.<\/jats:p>","DOI":"10.3390\/ijms22168816","type":"journal-article","created":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T21:27:45Z","timestamp":1629149265000},"page":"8816","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Endocytic Protein Defects in the Neural Crest Cell Lineage and Its Pathway Are Associated with Congenital Heart Defects"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1136-1085","authenticated-orcid":false,"given":"Angelo B.","family":"Arrigo","sequence":"first","affiliation":[{"name":"Department of Developmental Biology, University of Pittsburgh, Pittsburgh, PA 15224, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiuann-Huey Ivy","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, University of Pittsburgh, Pittsburgh, PA 15224, USA"},{"name":"Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA 15224, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/35025190","article-title":"A genetic blueprint for cardiac development","volume":"407","author":"Srivastava","year":"2000","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/s41569-018-0023-y","article-title":"Reassessing endothelial-to-mesenchymal transition in cardiovascular diseases","volume":"15","author":"Li","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1161\/CIRCRESAHA.109.201566","article-title":"Heart valve development: Regulatory networks in development and disease","volume":"105","author":"Combs","year":"2009","journal-title":"Circ. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.diff.2012.04.005","article-title":"The neural crest in cardiac congenital anomalies","volume":"84","author":"Keyte","year":"2012","journal-title":"Differentiation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1126\/science.6844926","article-title":"Neural crest cells contribute to normal aorticopulmonary septation","volume":"220","author":"Kirby","year":"1983","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"609","DOI":"10.4161\/cam.4.4.13489","article-title":"Factors controlling cardiac neural crest cell migration","volume":"4","author":"Kirby","year":"2010","journal-title":"Cell Adhes. Migr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1242\/dev.127.8.1607","article-title":"Fate of the mammalian cardiac neural crest","volume":"127","author":"Jiang","year":"2000","journal-title":"Development"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/bdrc.10002","article-title":"Neural crest and cardiovascular development: A 20-year perspective","volume":"69","author":"Hutson","year":"2003","journal-title":"Birth Defects Res. C Embryo Today"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1006\/dbio.1999.9219","article-title":"Connexin 43 expression reflects neural crest patterns during cardiovascular development","volume":"208","author":"Waldo","year":"1999","journal-title":"Dev. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"H1150","DOI":"10.1152\/ajpheart.00188.2016","article-title":"Cardiac neural crest ablation results in early endocardial cushion and hemodynamic flow abnormalities","volume":"311","author":"Ma","year":"2016","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1161\/01.CIR.0000023044.44974.8A","article-title":"Shortened outflow tract leads to altered cardiac looping after neural crest ablation","volume":"106","author":"Yelbuz","year":"2002","journal-title":"Circulation"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"169821","DOI":"10.1242\/dev.169821","article-title":"The diverse neural crest: From embryology to human pathology","volume":"146","author":"Etchevers","year":"2019","journal-title":"Development"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.resp.2015.09.017","article-title":"Multiple neural circuits mediating airway sensations: Recent advances in the neurobiology of the urge-to-cough","volume":"226","author":"Driessen","year":"2016","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1038\/ncomms2258","article-title":"Preotic neural crest cells contribute to coronary artery smooth muscle involving endothelin signalling","volume":"3","author":"Arima","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.jtcvs.2017.03.049","article-title":"Double-outlet right ventricle revisited","volume":"154","author":"Ebadi","year":"2017","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1002\/wdev.98","article-title":"Cardiac outflow tract anomalies","volume":"2","author":"Neeb","year":"2013","journal-title":"Wiley Interdiscip. Rev. Dev. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1161\/01.RES.0000202800.85341.6e","article-title":"Rotation of the myocardial wall of the outflow tract is implicated in the normal positioning of the great arteries","volume":"98","author":"Bajolle","year":"2006","journal-title":"Circ. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1002\/bdra.20308","article-title":"Racial differences in infant mortality attributable to birth defects in the United States, 1989\u20132002","volume":"76","author":"Yang","year":"2006","journal-title":"Birth Defects Res. A Clin. Mol. Teratol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1161\/CIRCULATIONAHA.115.019307","article-title":"Congenital Heart Defects in the United States: Estimating the Magnitude of the Affected Population in 2010","volume":"134","author":"Gilboa","year":"2016","journal-title":"Circulation"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1038\/nature14269","article-title":"Global genetic analysis in mice unveils central role for cilia in congenital heart disease","volume":"521","author":"Li","year":"2015","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1534\/genetics.109.112938","article-title":"The impact of whole genome sequencing on model system genetics: Get ready for the ride","volume":"184","author":"Hobert","year":"2010","journal-title":"Genetics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.cell.2005.06.032","article-title":"Role of endocytosis in cellular uptake of sex steroids","volume":"122","author":"Hammes","year":"2005","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4311","DOI":"10.1242\/dev.084467","article-title":"Endocytic receptor-mediated control of morphogen signaling","volume":"139","author":"Willnow","year":"2012","journal-title":"Development"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1161\/ATVBAHA.113.301924","article-title":"Low-density lipoprotein receptor-related protein-1: Role in the regulation of vascular integrity","volume":"34","author":"Strickland","year":"2014","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1007\/s00018-005-5231-z","article-title":"Molecular mechanisms of lipoprotein receptor signalling","volume":"62","author":"May","year":"2005","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1126\/science.1078124","article-title":"Structure of the LDL receptor extracellular domain at endosomal pH","volume":"298","author":"Rudenko","year":"2002","journal-title":"Science"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/s42003-020-1035-9","article-title":"Mutation of LRP1 in cardiac neural crest cells causes congenital heart defects by perturbing outflow lengthening","volume":"3","author":"Lin","year":"2020","journal-title":"Commun. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/0092-8674(92)90511-A","article-title":"LDL receptor-related protein internalizes and degrades uPA-PAI-1 complexes and is essential for embryo implantation","volume":"71","author":"Herz","year":"1992","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1038\/nbt1196-1562","article-title":"Sustained somatic gene inactivation by viral transfer of Cre recombinase","volume":"14","author":"Rohlmann","year":"1996","journal-title":"Nat. Biotechnol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1016\/S0960-9822(07)00562-3","article-title":"Modification of gene activity in mouse embryos in utero by a tamoxifen-inducible form of Cre recombinase","volume":"8","author":"Danielian","year":"1998","journal-title":"Curr. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.ydbio.2003.10.039","article-title":"Wnt1-Cre-mediated deletion of AP-2alpha causes multiple neural crest-related defects","volume":"267","author":"Brewer","year":"2004","journal-title":"Dev. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.ydbio.2005.08.041","article-title":"The right ventricle, outflow tract, and ventricular septum comprise a restricted expression domain within the secondary\/anterior heart field","volume":"287","author":"Verzi","year":"2005","journal-title":"Dev. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1006\/dbio.2000.0106","article-title":"Tie2-Cre transgenic mice: A new model for endothelial cell-lineage analysis in vivo","volume":"230","author":"Kisanuki","year":"2001","journal-title":"Dev. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/j.cell.2012.10.023","article-title":"Endocardial cells form the coronary arteries by angiogenesis through myocardial-endocardial VEGF signaling","volume":"151","author":"Wu","year":"2012","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0092-8674(03)00002-3","article-title":"Twist regulates cytokine gene expression through a negative feedback loop that represses NF-kappaB activity","volume":"112","author":"Richardson","year":"2003","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.devcel.2017.09.023","article-title":"Hemodynamic Forces Sculpt Developing Heart Valves through a KLF2-WNT9B Paracrine Signaling Axis","volume":"43","author":"Goddard","year":"2017","journal-title":"Dev. Cell"},{"key":"ref_37","first-page":"431","article-title":"Efficient Cre-mediated deletion in cardiac progenitor cells conferred by a 3\u2032UTR-ires-Cre allele of the homeobox gene Nkx2-5","volume":"46","author":"Stanley","year":"2002","journal-title":"Int. J. Dev. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3299","DOI":"10.1073\/pnas.0434590100","article-title":"Mapping Wnt\/beta-catenin signaling during mouse development and in colorectal tumors","volume":"100","author":"Maretto","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1083\/jcb.200403050","article-title":"Beta-catenin is required for endothelial-mesenchymal transformation during heart cushion development in the mouse","volume":"166","author":"Liebner","year":"2004","journal-title":"J. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/5007","article-title":"Generalized lacZ expression with the ROSA26 Cre reporter strain","volume":"21","author":"Soriano","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"78614","DOI":"10.18632\/oncotarget.20201","article-title":"Identification of LRP-1 as an endocytosis and recycling receptor for beta1-integrin in thyroid cancer cells","volume":"8","author":"Theret","year":"2017","journal-title":"Oncotarget"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.ydbio.2014.09.014","article-title":"Mesodermal expression of integrin alpha5beta1 regulates neural crest development and cardiovascular morphogenesis","volume":"395","author":"Liang","year":"2014","journal-title":"Dev. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5352","DOI":"10.1128\/MCB.00068-07","article-title":"Conditional deletion of focal adhesion kinase leads to defects in ventricular septation and outflow tract alignment","volume":"27","author":"Hakim","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.2353\/ajpath.2010.100213","article-title":"tPA activates LDL receptor-related protein 1-mediated mitogenic signaling involving the p90RSK and GSK3beta pathway","volume":"177","author":"Lin","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_45","first-page":"3821","article-title":"Tissue-type plasminogen activator promotes murine myofibroblast activation through LDL receptor-related protein 1-mediated integrin signaling","volume":"117","author":"Hu","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"18681","DOI":"10.1074\/jbc.M114.554584","article-title":"Yap1 is required for endothelial to mesenchymal transition of the atrioventricular cushion","volume":"289","author":"Zhang","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"15528","DOI":"10.1038\/s41598-017-14764-4","article-title":"Yes-Associated Protein (YAP) Promotes Tumorigenesis in Melanoma Cells Through Stimulation of Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1)","volume":"7","author":"Xiong","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"C1105","DOI":"10.1152\/ajpcell.00514.2002","article-title":"Identification of an apical sorting determinant in the cytoplasmic tail of megalin","volume":"284","author":"Takeda","year":"2003","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.devcel.2015.09.001","article-title":"LRP2 Acts as SHH Clearance Receptor to Protect the Retinal Margin from Mitogenic Stimuli","volume":"35","author":"Christ","year":"2015","journal-title":"Dev. Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.devcel.2011.11.023","article-title":"LRP2 is an auxiliary SHH receptor required to condition the forebrain ventral midline for inductive signals","volume":"22","author":"Christ","year":"2012","journal-title":"Dev. Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1242\/jcs.00313","article-title":"Megalin and the neurodevelopmental biology of sonic hedgehog and retinol","volume":"116","author":"McCarthy","year":"2003","journal-title":"J. Cell Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5557","DOI":"10.1073\/pnas.79.18.5557","article-title":"The pathogenic antigen of Heymann nephritis is a membrane glycoprotein of the renal proximal tubule brush border","volume":"79","author":"Kerjaschki","year":"1982","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"9725","DOI":"10.1073\/pnas.91.21.9725","article-title":"Complete cloning and sequencing of rat gp330\/\u201cmegalin,\u201d a distinctive member of the low density lipoprotein receptor gene family","volume":"91","author":"Saito","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"8460","DOI":"10.1073\/pnas.93.16.8460","article-title":"Defective forebrain development in mice lacking gp330\/megalin","volume":"93","author":"Willnow","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1093\/braincomms\/fcaa135","article-title":"Neuronal megalin mediates synaptic plasticity-a novel mechanism underlying intellectual disabilities in megalin gene pathologies","volume":"2","author":"Gomes","year":"2020","journal-title":"Brain Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.kint.2020.02.021","article-title":"Induced pluripotent stem cell-based disease modeling identifies ligand-induced decay of megalin as a cause of Donnai-Barrow syndrome","volume":"98","author":"Flemming","year":"2020","journal-title":"Kidney Int."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1167\/iovs.18-25667","article-title":"Selective Ablation of Megalin in the Retinal Pigment Epithelium Results in Megaophthalmos, Macromelanosome Formation and Severe Retina Degeneration","volume":"60","author":"Storm","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_58","first-page":"413","article-title":"Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development","volume":"9","author":"Baardman","year":"2016","journal-title":"Dis. Models Mech."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.1093\/hmg\/ddaa200","article-title":"LRP2 controls sonic hedgehog-dependent differentiation of cardiac progenitor cells during outflow tract formation","volume":"29","author":"Christ","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1242\/dev.02824","article-title":"Independent requirements for Hedgehog signaling by both the anterior heart field and neural crest cells for outflow tract development","volume":"134","author":"Goddeeris","year":"2007","journal-title":"Development"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/j.ajhg.2019.09.020","article-title":"Homozygous Loss-of-Function Mutations in AP1B1, Encoding Beta-1 Subunit of Adaptor-Related Protein Complex 1, Cause MEDNIK-like Syndrome","volume":"105","author":"Alsaif","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.neuron.2016.04.020","article-title":"Two Clathrin Adaptor Protein Complexes Instruct Axon-Dendrite Polarity","volume":"90","author":"Li","year":"2016","journal-title":"Neuron"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.conb.2018.02.021","article-title":"Neuronal functions of adaptor complexes involved in protein sorting","volume":"51","author":"Guardia","year":"2018","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1083\/jcb.201204072","article-title":"Control of vertebrate intraflagellar transport by the planar cell polarity effector Fuz","volume":"198","author":"Brooks","year":"2012","journal-title":"J. Cell Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1038\/ncb1966","article-title":"The planar cell polarity effector Fuz is essential for targeted membrane trafficking, ciliogenesis and mouse embryonic development","volume":"11","author":"Gray","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Wlodarczyk, B.J., Niederreither, K., Venugopalan, S., Florez, S., Finnell, R.H., and Amendt, B.A. (2011). Fuz regulates craniofacial development through tissue specific responses to signaling factors. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024608"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.devcel.2013.05.021","article-title":"Fuz mutant mice reveal shared mechanisms between ciliopathies and FGF-related syndromes","volume":"25","author":"Tabler","year":"2013","journal-title":"Dev. Cell"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4324","DOI":"10.1093\/hmg\/ddr359","article-title":"Mutations in the planar cell polarity gene, Fuzzy, are associated with neural tube defects in humans","volume":"20","author":"Seo","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1111\/tra.12152","article-title":"Nonmuscle myosin II is a critical regulator of clathrin-mediated endocytosis","volume":"15","author":"Chandrasekar","year":"2014","journal-title":"Traffic"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1161\/CIRCGENETICS.113.000455","article-title":"A point mutation in Myh10 causes major defects in heart development and body wall closure","volume":"7","author":"Ma","year":"2014","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1002\/dvdy.21101","article-title":"Microarray analysis of homocysteine-responsive genes in cardiac neural crest cells in vitro","volume":"236","author":"Rosenquist","year":"2007","journal-title":"Dev. Dyn."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.ydbio.2007.03.018","article-title":"The Hectd1 ubiquitin ligase is required for development of the head mesenchyme and neural tube closure","volume":"306","author":"Zohn","year":"2007","journal-title":"Dev. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e23343","DOI":"10.1002\/dvg.23343","article-title":"Reduced maternal vitamin A status increases the incidence of normal aortic arch variants","volume":"57","author":"Sugrue","year":"2019","journal-title":"Genesis"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.devcel.2009.12.019","article-title":"Retinoic acid regulates differentiation of the secondary heart field and TGFbeta-mediated outflow tract septation","volume":"18","author":"Li","year":"2010","journal-title":"Dev. Cell"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1002\/dvdy.24357","article-title":"Cardiac outflow morphogenesis depends on effects of retinoic acid signaling on multiple cell lineages","volume":"245","author":"Etchevers","year":"2016","journal-title":"Dev. Dyn."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/350473a0","article-title":"Regionally restricted developmental defects resulting from targeted disruption of the mouse homeobox gene hox-1.5","volume":"350","author":"Chisaka","year":"1991","journal-title":"Nature"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/8816\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:47:18Z","timestamp":1760165238000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/8816"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,16]]},"references-count":76,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["ijms22168816"],"URL":"https:\/\/doi.org\/10.3390\/ijms22168816","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,16]]}}}