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

Zhu L, Lee HO, Jordan CS, Cantrell VA, Southard-Smith EM, Shin MK
Nat Genet. 2004 36 (7): 732-7

PMID: 15170213 · DOI:10.1038/ng1371

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. One of the primary genes affected in HSCR encodes the G protein-coupled endothelin receptor-B (EDNRB). 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. 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, in the Ednrb ENS enhancer, and mutational analyses of these sites suggested that SOX10 may have multiple roles in regulating Ednrb in the ENS.

MeSH Terms (14)

Animals Base Sequence Enhancer Elements, Genetic Enteric Nervous System Gene Expression Regulation High Mobility Group Proteins Mice Mice, Transgenic Molecular Sequence Data Neoplasm Proteins Receptors, Endothelin Sequence Homology, Nucleic Acid SOXE Transcription Factors Transcription Factors

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