The endothelin receptor-B is required for the migration of neural crest-derived melanocyte and enteric neuron precursors

Lee, Hyung‐Ok; Levorse, John; Shin, Myung K.

doi:10.1016/s0012-1606(03)00160-x

Cited by 194 publications

(171 citation statements)

References 53 publications

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“…3d). Deleting 240 bp of intron 1 probably did not cause the ENS defect, as the same deletion was created previously with no effect on ENS expression 4,7 . It is possible, however, that the deletion of the endogenous promoter and 5′ untranslated region contributed to the ENS defect.…”

Section: E T T E R Smentioning

confidence: 76%

“…4a), and these progenitor cells had migratory defect in the distal ileum, rostral to the cecum, around E11.5 in Ednrb -/-and Sox10 +/-embryos (Fig. 4b) 7,8,15 . The decrease in the number of cells expressing Ednrb in Sox10 +/-embryos ( Fig.…”

Section: E T T E R Smentioning

confidence: 97%

“…Ednrb is expressed as early as E9.5 in ENS precursors, and expression is maintained in the developing gut during embryogenesis (Fig. 2e) 7 . We analyzed four stable lines from the -1.2-kb Ednrb-LacZ (Fig.…”

Section: E T T E R Smentioning

confidence: 99%

“…4), when vagal neural crest-derived ENS progenitors are populating the hindgut during mouse embryogenesis, such that in the absence of EDNRB the migratory wavefront is delayed near the ileocecal junction (Fig. 1a) [6][7][8] . To elucidate the molecular mechanisms for Ednrb expression in the ENS, we dissected the Ednrb genomic region.…”

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Spatiotemporal regulation of endothelin receptor-B by SOX10 in neural crest–derived enteric neuron precursors

et al. 2004

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Hirschsprung disease (HSCR) is a multigenic, congenital disorder that affects 1 in 5,000 newborns and is characterized by the absence of neural crest-derived enteric ganglia in the colon 1 . One of the primary genes affected in HSCR encodes the G protein-coupled endothelin receptor-B (EDNRB) 2,3 . The expression of Ednrb is required at a defined time period during the migration of the precursors of the enteric nervous system (ENS) into the colon 4 . In this study, we describe a conserved spatiotemporal ENS enhancer of Ednrb. This 1-kb enhancer is activated as the ENS precursors approach the colon, and partial deletion of this enhancer at the endogenous Ednrb locus results in pigmented mice that die postnatally from megacolon. We identified binding sites for SOX10, an SRY-related transcription factor associated with HSCR 5 , in the Ednrb ENS enhancer, and mutational analyses of these sites suggested that SOX10 may have multiple roles in regulating Ednrb in the ENS.Mice and individuals with HSCR with mutations in the EDNRB-mediated pathway have megacolon because of the absence of enteric neurons in the distal gut 1 . This regional specificity of aganglionosis could be explained by a temporal requirement for Ednrb between embryonic day (E) 11 and E12.5 (ref. 4), when vagal neural crest-derived ENS progenitors are populating the hindgut during mouse embryogenesis, such that in the absence of EDNRB the migratory wavefront is delayed near the ileocecal junction (Fig. 1a) [6][7][8] . To elucidate the molecular mechanisms for Ednrb expression in the ENS, we dissected the Ednrb genomic region. We isolated a 78-kb P1 genomic clone encompassing Ednrb (Fig. 1b) and used it to create four independent transgenic lines. When we crossed the individual transgenic lines into the Ednrb-null mice, all the lines rescued postnatal death from megacolon (Fig. 1c). Although three of the lines did not rescue the melanocyte defect in the Ednrb-null mice (Fig. 1c), one line (when homozygous with respect to the transgene) partially rescued the pigmentation defect that resembles the hypomorphic Ednrb s allele 9 (data not shown). These results suggested that the P1 clone contained the necessary information for expression of Ednrb in ENS progenitors. In addition, we mapped a main transcription start site Ednrb -/-Tg P5

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Section: E T T E R Smentioning

confidence: 76%

Section: E T T E R Smentioning

confidence: 97%

Section: E T T E R Smentioning

confidence: 99%

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confidence: 99%

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Spatiotemporal regulation of endothelin receptor-B by SOX10 in neural crest–derived enteric neuron precursors

et al. 2004

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“…Endothelins are a family of peptides comprising potent vasoconstrictors, which are primaliry expressed by the endothelium (Agapitov and Haynes, 2002). NC cells, which invade the developing gut express Endothelin receptor type B (EDNRB), while Edn3 is expressed in the midgut and hindgut mesoderm as well as in the caecum and proximal colon (Barlow et al, 2003, Leibl et al, 1999.2.1) In mouse, mutations in Edn3 and EDNRB cause delayed migration of gut-destinated NC cells (Barlow et al, 2003;Lee et al, 2003;Ro et al, 2006). Another factor, which has been proposed to attract NC cells is stromal derived factor-1 (Sdf1), a secreted protein which binds transmembrane receptor CXCR4.…”

Section: Guiding Signals-attractantsmentioning

confidence: 99%