Open AccessRetinoic Acid Repression of Bone Morphogenetic Protein 4 in Inner Ear Development
Author(s) -
Deborah Thompson,
Lisa M. Gerlach-Bank,
Kate F. Barald,
Ronald J. Koenig
Publication year - 2003
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.23.7.2277-2286.2003
Subject(s) - retinoic acid , biology , bone morphogenetic protein 4 , inner ear , microbiology and biotechnology , bone morphogenetic protein , retinoic acid receptor beta , retinoic acid receptor gamma , retinoic acid inducible orphan g protein coupled receptor , psychological repression , transcription factor , retinoic acid receptor , anatomy , genetics , gene , gene expression
Bone morphogenetic protein 4 (BMP4) and retinoic acid are important for normal development of the inner ear, but whether they are linked mechanistically is not known. BMP4 antagonists disrupt semicircular canal formation, as does exposure to retinoic acid. We demonstrate that retinoic acid directly down-regulates BMP4 transcription in a mouse inner ear-derived cell line, and we identify a novel promoter in the second intron of the BMP4 gene that is a target of this regulation both in the cell line and in the mouse embryonic inner ear in vivo. The importance of this down-regulation is demonstrated in chicken embryos by showing that the retinoic acid effect on semicircular canal development can be overcome by exogenous BMP4.