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Crk ‐associated substrate (Cas) family member, NEDD9 , is regulated in human neuroblastoma cells and in the embryonic hindbrain by all‐ trans retinoic acid
Author(s) -
Merrill Ronald A.,
See Angela WaiMan,
Wertheim Margaret L.,
ClagettDame Margaret
Publication year - 2004
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.20159
Subject(s) - retinoic acid , biology , rhombomere , hindbrain , adapter molecule crk , microbiology and biotechnology , retinoic acid receptor gamma , retinoic acid inducible orphan g protein coupled receptor , retinoic acid receptor alpha , retinoic acid receptor , tretinoin , cell culture , signal transduction , embryo , gene expression , biochemistry , genetics , hox gene , gene , signal transducing adaptor protein
The vitamin A metabolite, all‐ trans retinoic acid (atRA), plays an essential role in vertebrate embryogenesis, including development of the nervous system. In the human neuroblastoma cell line, SH‐SY5Y, atRA rapidly induces (within 4 hr) the expression of the Crk‐associated substrate (Cas) family member, n eural precursor cell‐ e xpressed, d evelopmentally d own‐regulated gene 9 ( NEDD9 ) also called the h uman e nhancer of f ilamentation ( HEF1 ). NEDD9 is expressed in the developing hindbrain (5‐somite stage) in the presumptive rhombomeres 2, 3, and 5 before the onset of overt segmentation. Exposure of rat embryos to excess atRA at times ranging from E9.25 to E12 leads to altered NEDD9 expression in the developing hindbrain within 6 hr. NEDD9 expression is also perturbed in vitamin A‐deficient embryos. A putative retinoic acid response element in the 5′ region of the NEDD9 promoter binds specifically to a RXR/RAR heterodimer and forms a higher molecular weight complex upon addition of a retinoic acid receptor‐specific antibody. Regulation of NEDD9 may be an important means whereby atRA promotes cell spreading and neurite outgrowth in SH‐SY5Y human neuroblastoma cells, and NEDD9 represents a new downstream target of atRA and its receptors in the developing hindbrain. Developmental Dynamics 231:564–575, 2004. © 2004 Wiley‐Liss, Inc.