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Article: Perturbation of Hoxb5 signaling in vagal and trunk neural crest cells causes apoptosis and neurocristopathies in mice

TitlePerturbation of Hoxb5 signaling in vagal and trunk neural crest cells causes apoptosis and neurocristopathies in mice
Authors
KeywordsSox9
neurocristopathies
neural crest cells
Hoxb5
Issue Date2014
Citation
Cell Death and Differentiation, 2014, v. 21, n. 2, p. 278-289 How to Cite?
AbstractNeural crest cells (NCCs) migrate from different regions along the anterior-posterior axis of the neural tube (NT) to form different structures. Defective NCC development causes congenital neurocristopathies affecting multiple NCC-derived tissues in human. Perturbed Hoxb5 signaling in vagal NCC causes enteric nervous system (ENS) defects. This study aims to further investigate if perturbed Hoxb5 signaling in trunk NCC contributes to defects of other NCC-derived tissues besides the ENS. We perturbed Hoxb5 signaling in NCC from the entire NT, and investigated its impact in the development of tissues derived from these cells in mice. Perturbation of Hoxb5 signaling in these NCC resulted in Sox9 downregulation, NCC apoptosis, hypoplastic sympathetic and dorsal root ganglia, hypopigmentation and ENS defects. Mutant mice with NCC-specific Sox9 deletion also displayed some of these phenotypes. In vitro and in vivo assays indicated that the Sox9 promoter was bound and trans-activated by Hoxb5. In ovo studies further revealed that Sox9 alleviated apoptosis induced by perturbed Hoxb5 signaling, and Hoxb5 induced ectopic Sox9 expression in chick NT. This study demonstrates that Hoxb5 regulates Sox9 expression in NCC and disruption of this signaling causes Sox9 downregulation, NCC apoptosis and multiple NCC-developmental defects. Phenotypes such as ENS deficiency, hypopigmentation and some of the neurological defects are reported in patients with Hirschsprung disease (HSCR). Whether dysregulation of Hoxb5 signaling and early depletion of NCC contribute to ENS defect and other neurocristopathies in HSCR patients deserves further investigation. © 2014 Macmillan Publishers Limited.
Persistent Identifierhttp://hdl.handle.net/10722/220755
ISSN
2015 Impact Factor: 8.218
2015 SCImago Journal Rankings: 4.219
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorKam, M. K M-
dc.contributor.authorCheung, M. C H-
dc.contributor.authorZhu, J. J.-
dc.contributor.authorCheng, W. W C-
dc.contributor.authorSat, E. W Y-
dc.contributor.authorTam, P. K H-
dc.contributor.authorLui, V. C H-
dc.date.accessioned2015-10-16T06:50:27Z-
dc.date.available2015-10-16T06:50:27Z-
dc.date.issued2014-
dc.identifier.citationCell Death and Differentiation, 2014, v. 21, n. 2, p. 278-289-
dc.identifier.issn1350-9047-
dc.identifier.issn1350-9047-
dc.identifier.urihttp://hdl.handle.net/10722/220755-
dc.description.abstractNeural crest cells (NCCs) migrate from different regions along the anterior-posterior axis of the neural tube (NT) to form different structures. Defective NCC development causes congenital neurocristopathies affecting multiple NCC-derived tissues in human. Perturbed Hoxb5 signaling in vagal NCC causes enteric nervous system (ENS) defects. This study aims to further investigate if perturbed Hoxb5 signaling in trunk NCC contributes to defects of other NCC-derived tissues besides the ENS. We perturbed Hoxb5 signaling in NCC from the entire NT, and investigated its impact in the development of tissues derived from these cells in mice. Perturbation of Hoxb5 signaling in these NCC resulted in Sox9 downregulation, NCC apoptosis, hypoplastic sympathetic and dorsal root ganglia, hypopigmentation and ENS defects. Mutant mice with NCC-specific Sox9 deletion also displayed some of these phenotypes. In vitro and in vivo assays indicated that the Sox9 promoter was bound and trans-activated by Hoxb5. In ovo studies further revealed that Sox9 alleviated apoptosis induced by perturbed Hoxb5 signaling, and Hoxb5 induced ectopic Sox9 expression in chick NT. This study demonstrates that Hoxb5 regulates Sox9 expression in NCC and disruption of this signaling causes Sox9 downregulation, NCC apoptosis and multiple NCC-developmental defects. Phenotypes such as ENS deficiency, hypopigmentation and some of the neurological defects are reported in patients with Hirschsprung disease (HSCR). Whether dysregulation of Hoxb5 signaling and early depletion of NCC contribute to ENS defect and other neurocristopathies in HSCR patients deserves further investigation. © 2014 Macmillan Publishers Limited.-
dc.languageeng-
dc.relation.ispartofCell Death and Differentiation-
dc.subjectSox9-
dc.subjectneurocristopathies-
dc.subjectneural crest cells-
dc.subjectHoxb5-
dc.titlePerturbation of Hoxb5 signaling in vagal and trunk neural crest cells causes apoptosis and neurocristopathies in mice-
dc.typeArticle-
dc.description.natureLink_to_subscribed_fulltext-
dc.identifier.doi10.1038/cdd.2013.142-
dc.identifier.pmid24141719-
dc.identifier.pmcidPMC3890950-
dc.identifier.scopuseid_2-s2.0-84892436430-
dc.identifier.hkuros226978-
dc.identifier.volume21-
dc.identifier.issue2-
dc.identifier.spage278-
dc.identifier.epage289-
dc.identifier.eissn1476-5403-
dc.identifier.isiWOS:000329787800013-

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