{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T20:40:01Z","timestamp":1788381601488,"version":"build-2803163510"},"reference-count":77,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T00:00:00Z","timestamp":1630972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Theme-Based Research Scheme","award":["T12C-714\/14-R"],"award-info":[{"award-number":["T12C-714\/14-R"]}]},{"name":"Commissioned Paediatric Research at Hong Kong Children\u2019s Hospital","award":["PR-HKU-1"],"award-info":[{"award-number":["PR-HKU-1"]}]},{"name":"General Research Fund","award":["17113420"],"award-info":[{"award-number":["17113420"]}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["06171636"],"award-info":[{"award-number":["06171636"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The development of the enteric nervous system (ENS) is highly modulated by the synchronized interaction between the enteric neural crest cells (ENCCs) and the neural stem cell niche comprising the gut microenvironment. Genetic defects dysregulating the cellular behaviour(s) of the ENCCs result in incomplete innervation and hence ENS dysfunction. Hirschsprung disease (HSCR) is a rare complex neurocristopathy in which the enteric neural crest-derived cells fail to colonize the distal colon. In addition to ENS defects, increasing evidence suggests that HSCR patients may have intrinsic defects in the niche impairing the extracellular matrix (ECM)-cell interaction and\/or dysregulating the cellular niche factors necessary for controlling stem cell behaviour. The niche defects in patients may compromise the regenerative capacity of the stem cell-based therapy and advocate for drug- and niche-based therapies as complementary therapeutic strategies to alleviate\/enhance niche-cell interaction. Here, we provide a summary of the current understandings of the role of the enteric neural stem cell niche in modulating the development of the ENS and in the pathogenesis of HSCR. Deciphering the contribution of the niche to HSCR may provide important implications to the development of regenerative medicine for HSCR.<\/jats:p>","DOI":"10.3390\/ijms22189659","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T23:55:22Z","timestamp":1630972522000},"page":"9659","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Roles of Enteric Neural Stem Cell Niche and Enteric Nervous System Development in Hirschsprung Disease"],"prefix":"10.3390","volume":"22","author":[{"given":"Yue","family":"Ji","sequence":"first","affiliation":[{"name":"Li Dak-Sum Research Centre, The University of Hong Kong\u2014Karolinska Institutet Collaboration in Regenerative Medicine, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul Kwong-Hang","family":"Tam","sequence":"additional","affiliation":[{"name":"Li Dak-Sum Research Centre, The University of Hong Kong\u2014Karolinska Institutet Collaboration in Regenerative Medicine, Hong Kong, China"},{"name":"Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0265-2638","authenticated-orcid":false,"given":"Clara Sze-Man","family":"Tang","sequence":"additional","affiliation":[{"name":"Li Dak-Sum Research Centre, The University of Hong Kong\u2014Karolinska Institutet Collaboration in Regenerative Medicine, Hong Kong, China"},{"name":"Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nrgastro.2016.107","article-title":"The bowel and beyond: The enteric nervous system in neurological disorders","volume":"13","author":"Rao","year":"2016","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e13234","DOI":"10.1111\/nmo.13234","article-title":"The first brain: Species comparisons and evolutionary implications for the enteric and central nervous systems","volume":"30","author":"Furness","year":"2018","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1038\/s41583-018-0041-0","article-title":"Enteric nervous system development: What could possibly go wrong?","volume":"19","author":"Rao","year":"2018","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s00383-009-2402-2","article-title":"Genetic basis of Hirschsprung\u2019s disease","volume":"25","author":"Tam","year":"2009","journal-title":"Pediatric Surg. Int."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Puri, P. (2019). Genetics of Hirschsprung\u2019s Disease. Hirschsprung\u2019s Disease and Allied Disorders, Springer International Publishing.","DOI":"10.1007\/978-3-642-38482-0_75-2"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/jmg.2007.053959","article-title":"Hirschsprung disease, associated syndromes and genetics: A review","volume":"45","author":"Amiel","year":"2008","journal-title":"J. Med. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s00383-017-4202-4","article-title":"Are all patients with short segment Hirschsprung\u2019s disease equal? A retrospective multicenter study","volume":"34","author":"Chung","year":"2018","journal-title":"Pediatr. Surg. Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jpedsurg.2015.10.021","article-title":"Hirschsprung\u2019s disease: A bridge for science and surgery","volume":"51","author":"Tam","year":"2016","journal-title":"J. Pediatr. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.ydbio.2016.04.001","article-title":"White paper on guidelines concerning enteric nervous system stem cell therapy for enteric neuropathies","volume":"417","author":"Burns","year":"2016","journal-title":"Dev. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e12993","DOI":"10.1111\/nmo.12993","article-title":"Recent advances in regenerative medicine to treat enteric neuropathies: Use of human cells","volume":"29","author":"Stamp","year":"2017","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1053\/j.gastro.2017.03.014","article-title":"Correction of Hirschsprung-Associated Mutations in Human Induced Pluripotent Stem Cells via Clustered Regularly Interspaced Short Palindromic Repeats\/Cas9, Restores Neural Crest Cell Function","volume":"153","author":"Lai","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nature16951","article-title":"Deriving human ENS lineages for cell therapy and drug discovery in Hirschsprung disease","volume":"531","author":"Fattahi","year":"2016","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e12900","DOI":"10.1111\/nmo.12900","article-title":"In vivo transplantation of fetal human gut-derived enteric neural crest cells","volume":"29","author":"Cooper","year":"2017","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.stemcr.2020.07.024","article-title":"Retinoic Acid Accelerates the Specification of Enteric Neural Progenitors from In-Vitro-Derived Neural Crest","volume":"15","author":"Frith","year":"2020","journal-title":"Stem Cell Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11980","DOI":"10.1073\/pnas.1710308114","article-title":"Dual origin of enteric neurons in vagal Schwann cell precursors and the sympathetic neural crest","volume":"114","author":"Jevans","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/dvdy.10350","article-title":"HOXB5 expression is spatially and temporarily regulated in human embryonic gut during neural crest cell colonization and differentiation of enteric neuroblasts","volume":"228","author":"Fu","year":"2003","journal-title":"Dev. Dyn."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/nrn2137","article-title":"Enteric nervous system development and Hirschsprung\u2019s disease: Advances in genetic and stem cell studies","volume":"8","author":"Heanue","year":"2007","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s00441-020-03262-1","article-title":"Intracellular RET signaling pathways activated by GDNF","volume":"382","author":"Kawai","year":"2020","journal-title":"Cell Tissue Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/nrgastro.2012.234","article-title":"Development and developmental disorders of the enteric nervous system","volume":"10","author":"Obermayr","year":"2013","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S156","DOI":"10.1016\/j.ydbio.2018.08.014","article-title":"News from the endothelin-3\/EDNRB signaling pathway: Role during enteric nervous system development and involvement in neural crest-associated disorders","volume":"444","author":"Bondurand","year":"2018","journal-title":"Dev. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1242\/dev.00433","article-title":"GDNF availability determines enteric neuron number by controlling precursor proliferation","volume":"130","author":"Gianino","year":"2003","journal-title":"Development"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"16372","DOI":"10.1523\/JNEUROSCI.2079-13.2013","article-title":"GDNF signaling levels control migration and neuronal differentiation of enteric ganglion precursors","volume":"33","author":"Uesaka","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1053\/j.gastro.2020.07.018","article-title":"Glial Cell-Derived Neurotrophic Factor Induces Enteric Neurogenesis and Improves Colon Structure and Function in Mouse Models of Hirschsprung Disease","volume":"159","author":"Soret","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1053\/j.gastro.2016.12.034","article-title":"Differentiation of Mouse Enteric Nervous System Progenitor Cells Is Controlled by Endothelin 3 and Requires Regulation of Ednrb by SOX10 and ZEB2","volume":"152","author":"Watanabe","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.ydbio.2006.01.032","article-title":"Endothelin-3 regulates neural crest cell proliferation and differentiation in the hindgut enteric nervous system","volume":"293","author":"Nagy","year":"2006","journal-title":"Dev. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/S0896-6273(03)00730-X","article-title":"Enteric nervous system progenitors are coordinately controlled by the G protein-coupled receptor EDNRB and the receptor tyrosine kinase RET","volume":"40","author":"Barlow","year":"2003","journal-title":"Neuron"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1006\/dbio.1998.8876","article-title":"GDNF and ET-3 differentially modulate the numbers of avian enteric neural crest cells and enteric neurons in vitro","volume":"197","author":"Hearn","year":"1998","journal-title":"Dev. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1242\/dev.02375","article-title":"Maintenance of mammalian enteric nervous system progenitors by SOX10 and endothelin 3 signalling","volume":"133","author":"Bondurand","year":"2006","journal-title":"Development"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"37877","DOI":"10.1038\/srep37877","article-title":"Endothelin-3 stimulates cell adhesion and cooperates with \u03b21-integrins during enteric nervous system ontogenesis","volume":"6","author":"Gazquez","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1006\/dbio.1996.0234","article-title":"Increased expression of laminin-1 and collagen (IV) subunits in the aganglionic bowel of ls\/ls, but not c-ret \u2212\/\u2212 mice","volume":"178","author":"Rothman","year":"1996","journal-title":"Dev. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1053\/j.gastro.2018.09.012","article-title":"Identification of Genes Associated With Hirschsprung Disease, Based on Whole-Genome Sequence Analysis, and Potential Effects on Enteric Nervous System Development","volume":"155","author":"Tang","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/ng1196-345","article-title":"Germline mutations of the RET ligand GDNF are not sufficient to cause Hirschsprung disease","volume":"14","author":"Salomon","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1056\/NEJMoa1706594","article-title":"Molecular Genetic Anatomy and Risk Profile of Hirschsprung\u2019s Disease","volume":"380","author":"Tilghman","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1053\/j.gastro.2018.03.034","article-title":"Identification of Variants in RET and IHH Pathway Members in a Large Family With History of Hirschsprung Disease","volume":"155","author":"Sribudiani","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2694","DOI":"10.1073\/pnas.0809630105","article-title":"Genome-wide association study identifies NRG1 as a susceptibility locus for Hirschsprung\u2019s disease","volume":"106","author":"Tang","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.ajhg.2015.02.014","article-title":"Functional loss of semaphorin 3C and\/or semaphorin 3D and their epistatic interaction with ret are critical to Hirschsprung disease liability","volume":"96","author":"Jiang","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1093\/hmg\/ddv051","article-title":"Population variation in total genetic risk of Hirschsprung disease from common RET, SEMA3 and NRG1 susceptibility polymorphisms","volume":"24","author":"Kapoor","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1038\/jhg.2012.18","article-title":"Association of genetic polymorphisms in the RET-protooncogene and NRG1 with Hirschsprung disease in Thai patients","volume":"57","author":"Phusantisampan","year":"2012","journal-title":"J. Hum. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Tang, C.S.-M., Tang, W.-K., So, M.-T., Miao, X.-P., Leung, B.M.-C., Yip, B.H.-K., Leon, T.Y.-Y., Ngan, E.S.-W., Lui, V.C.-H., and Chen, Y. (2011). Fine Mapping of the NRG1 Hirschsprung\u2019s Disease Locus. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016181"},{"key":"ref_40","first-page":"5265","article-title":"Trans-ethnic meta-analysis of genome-wide association studies for Hirschsprung disease","volume":"25","author":"Tang","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/s41431-017-0053-7","article-title":"Genome-wide association study of Hirschsprung disease detects a novel low-frequency variant at the RET locus","volume":"26","author":"Fadista","year":"2018","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Le, T.-L., Galmiche, L., Levy, J., Suwannarat, P., Hellebrekers, D.M.E.I., Morarach, K., Boismoreau, F., Theunissen, T.E.J., Lefebvre, M., and Pelet, A. (2021). Dysregulation of the NRG1\/ERBB pathway causes a developmental disorder with gastrointestinal dysmotility in humans. J. Clin. Investig., 131.","DOI":"10.1172\/JCI145837"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s00439-011-1035-4","article-title":"Mutations in the NRG1 gene are associated with Hirschsprung disease","volume":"131","author":"Tang","year":"2012","journal-title":"Hum. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1007\/s12035-012-8392-4","article-title":"Exome sequencing identified NRG3 as a novel susceptible gene of Hirschsprung\u2019s disease in a Chinese population","volume":"47","author":"Yang","year":"2013","journal-title":"Mol. Neurobiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/s00439-013-1272-9","article-title":"RET and NRG1 interplay in Hirschsprung disease","volume":"132","author":"Gui","year":"2013","journal-title":"Hum. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1002\/glia.20753","article-title":"Neuregulin-1, a key axonal signal that drives Schwann cell growth and differentiation","volume":"56","author":"Birchmeier","year":"2008","journal-title":"Glia"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/j.semcdb.2010.08.008","article-title":"Nrg1\/ErbB signaling networks in Schwann cell development and myelination","volume":"21","author":"Newbern","year":"2010","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9879","DOI":"10.1523\/JNEUROSCI.1239-15.2015","article-title":"Neuronal Differentiation in Schwann Cell Lineage Underlies Postnatal Neurogenesis in the Enteric Nervous System","volume":"35","author":"Uesaka","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2575","DOI":"10.1002\/glia.24059","article-title":"Enhanced enteric neurogenesis by Schwann cell precursors in mouse models of Hirschsprung disease","volume":"69","author":"Uesaka","year":"2021","journal-title":"Glia"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.stem.2020.11.008","article-title":"Mapping Development of the Human Intestinal Niche at Single-Cell Resolution","volume":"28","author":"Holloway","year":"2021","journal-title":"Cell Stem Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.stem.2020.06.021","article-title":"Mesenchymal Niche-Derived Neuregulin-1 Drives Intestinal Stem Cell Proliferation and Regeneration of Damaged Epithelium","volume":"27","author":"Chan","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Luz\u00f3n-Toro, B., Fern\u00e1ndez, R.M., Torroglosa, A., de Agust\u00edn, J.C., M\u00e9ndez-Vidal, C., Segura, D.I., Anti\u00f1olo, G., and Borrego, S. (2013). Mutational spectrum of semaphorin 3A and semaphorin 3D genes in Spanish Hirschsprung patients. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054800"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6919","DOI":"10.1073\/pnas.0602152103","article-title":"Expression profiling the developing mammalian enteric nervous system identifies marker and candidate Hirschsprung disease genes","volume":"103","author":"Heanue","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1101\/gr.264473.120","article-title":"Whole-genome analysis of noncoding genetic variations identifies multi-scale regulatory element perturbations associated with Hirschsprung disease","volume":"30","author":"Fu","year":"2020","journal-title":"Genome Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e145854","DOI":"10.1172\/jci.insight.145854","article-title":"Cell-autonomous retinoic acid receptor signaling has stage-specific effects on mouse enteric nervous system","volume":"6","author":"Gao","year":"2021","journal-title":"JCI Insight"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1242\/dev.040550","article-title":"Vitamin A facilitates enteric nervous system precursor migration by reducing Pten accumulation","volume":"137","author":"Fu","year":"2010","journal-title":"Development"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1016\/S0140-6736(17)32284-5","article-title":"Advances in paediatric gastroenterology","volume":"390","author":"Tam","year":"2017","journal-title":"Lancet"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1016\/0016-5085(92)90761-M","article-title":"Abnormalities in the distribution of laminin and collagen type IV in Hirschsprung\u2019s disease","volume":"102","author":"Parikh","year":"1992","journal-title":"Gastroenterology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1016\/0022-3468(94)90101-5","article-title":"The extracellular matrix components, tenascin and fibronectin, in Hirschsprung\u2019s disease: An immunohistochemical study","volume":"29","author":"Parikh","year":"1994","journal-title":"J. Pediatr. Surg."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/0022-3468(92)90545-I","article-title":"Quantitative and qualitative analysis of the extracellular matrix protein, laminin, in Hirschsprung\u2019s disease","volume":"27","author":"Parikh","year":"1992","journal-title":"J. Pediatr. Surg."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e13134","DOI":"10.1111\/nmo.13134","article-title":"Down-regulation of fibronectin and the correlated expression of neuroligin in hirschsprung disease","volume":"29","author":"Zheng","year":"2017","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1007\/s10571-019-00759-4","article-title":"Increased Fibronectin Impairs the Function of Excitatory\/Inhibitory Synapses in Hirschsprung Disease","volume":"40","author":"Gao","year":"2020","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1097\/MPG.0000000000002627","article-title":"Aberrant Distributions of Collagen I, III, and IV in Hirschsprung Disease","volume":"70","author":"Gao","year":"2020","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/0012-1606(88)90217-5","article-title":"Accumulation of components of basal laminae: Association with the failure of neural crest cells to colonize the presumptive aganglionic bowel of ls\/ls mutant mice","volume":"125","author":"Payette","year":"1988","journal-title":"Dev. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3195","DOI":"10.1242\/dev.031302","article-title":"Age-dependent changes in the gut environment restrict the invasion of the hindgut by enteric neural progenitors","volume":"136","author":"Druckenbrod","year":"2009","journal-title":"Development"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1242\/dev.02346","article-title":"Lack of beta1 integrins in enteric neural crest cells leads to a Hirschsprung-like phenotype","volume":"133","author":"Breau","year":"2006","journal-title":"Development"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S0092-8674(02)00971-6","article-title":"Integrins: Bidirectional, allosteric signaling machines","volume":"110","author":"Hynes","year":"2002","journal-title":"Cell"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1002\/glia.20536","article-title":"Alpha7beta1 integrin is a receptor for laminin-2 on Schwann cells","volume":"55","author":"Chernousov","year":"2007","journal-title":"Glia"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.ydbio.2009.03.025","article-title":"Endothelial cells promote migration and proliferation of enteric neural crest cells via beta1 integrin signaling","volume":"330","author":"Nagy","year":"2009","journal-title":"Dev. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.ydbio.2013.08.006","article-title":"Enteric neural crest-derived cells promote their migration by modifying their microenvironment through tenascin-C production","volume":"382","author":"Akbareian","year":"2013","journal-title":"Dev. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"dev160317","DOI":"10.1242\/dev.160317","article-title":"Collagen 18 and agrin are secreted by neural crest cells to remodel their microenvironment and regulate their migration during enteric nervous system development","volume":"145","author":"Nagy","year":"2018","journal-title":"Development"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4483","DOI":"10.1172\/JCI83178","article-title":"A collagen VI\u2013dependent pathogenic mechanism for Hirschsprung\u2019s disease","volume":"125","author":"Soret","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2791","DOI":"10.1242\/dev.031419","article-title":"Beta1 integrins are required for the invasion of the caecum and proximal hindgut by enteric neural crest cells","volume":"136","author":"Breau","year":"2009","journal-title":"Development"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1016\/j.bbrc.2017.11.184","article-title":"Collagen VI suppresses fibronectin-induced enteric neural crest cell migration by downregulation of focal adhesion proteins","volume":"495","author":"Nishida","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/s41431-018-0129-z","article-title":"Uncovering the genetic lesions underlying the most severe form of Hirschsprung disease by whole-genome sequencing","volume":"26","author":"Tang","year":"2018","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"13422","DOI":"10.1523\/JNEUROSCI.1764-14.2014","article-title":"FAK is required for Schwann cell spreading on immature basal lamina to coordinate the radial sorting of peripheral axons with myelination","volume":"34","author":"Grove","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"17292","DOI":"10.1074\/jbc.M110.168500","article-title":"Focal adhesion kinase (FAK) binds RET kinase via its FERM domain, priming a direct and reciprocal RET-FAK transactivation mechanism","volume":"286","author":"Morandi","year":"2011","journal-title":"J. Biol. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/18\/9659\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:57:42Z","timestamp":1760165862000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/18\/9659"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,7]]},"references-count":77,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["ijms22189659"],"URL":"https:\/\/doi.org\/10.3390\/ijms22189659","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,7]]}}}