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Targeting of endothelin receptor‐B to the neural crest
Author(s) -
Druckenbrod Noah R.,
Powers Patricia A.,
Bartley Christopher R.,
Walker Jeffery W.,
Epstein Miles L.
Publication year - 2008
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/dvg.20415
Subject(s) - neural crest , biology , receptor , phenotype , microbiology and biotechnology , downregulation and upregulation , genetics , gene
Endothelin receptor B (Ednrb) plays a critical role in the development of melanocytes and neurons and glia of the enteric nervous system. These distinct neural crest‐derived cell types express Ednrb and share the property of intercalating into tissues, such as the intestine whose muscle precursor cells also express Ednrb. Such widespread Ednrb expression has been a significant obstacle in establishing precise roles for Ednrb in development. We describe here the production of an Ednrb allele floxed at exon 3 and its use in excising the receptor from mouse neural crest cells by use of Cre‐recombinase driven by the Wnt1 promoter. Mice born with neural crest‐specific excision of Ednrb possess aganglionic colon, lack trunk pigmentation, and die within 5 weeks due to megacolon. Ednrb receptor expression in these animals is absent only in the neural crest but present in surrounding smooth muscle cells. The absence of Ednrb from crest cells also results in a compensatory upregulation of Ednrb expression in other cells within the gut. We conclude that Ednrb loss only in neural crest cells is sufficient to produce the Hirschsprungs disease phenotype observed with genomic Ednrb mutations. genesis 46:396–400, 2008. © 2008 Wiley‐Liss, Inc.