Journal
NATURE GENETICS
Volume 36, Issue 7, Pages 732-737Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng1371
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Funding
- NIDDK NIH HHS [R01 DK060047-01A1, R01 DK060047-02, R01 DK060047, R01 DK060047-03] Funding Source: Medline
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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 HSCR5, in the Ednrb ENS enhancer, and mutational analyses of these sites suggested that SOX10 may have multiple roles in regulating Ednrb in the ENS.
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