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Retinoic acid specifically downregulates Fgf4 and inhibits posterior cell proliferation in the developing mouse autopod
Author(s) -
HAYES CHRISTOPHER,
MORRISSKAY GILLIAN M.
Publication year - 2001
Publication title -
journal of anatomy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 118
eISSN - 1469-7580
pISSN - 0021-8782
DOI - 10.1046/j.1469-7580.2001.19850561.x
Subject(s) - zone of polarizing activity , retinoic acid , limb bud , apical ectodermal ridge , mesenchyme , biology , limb development , sonic hedgehog , downregulation and upregulation , tretinoin , endocrinology , retinoid , microbiology and biotechnology , medicine , fgf8 , mesenchymal stem cell , mesoderm , receptor , signal transduction , genetics , embryonic stem cell , fibroblast growth factor , gene , embryo
Retinoic acid, when administered to pregnant mice on d 11·0 of gestation, causes limb skeletal abnormalities consisting of reduced digital number, shortening of the long bones and delayed ossification. We show here that these effects are correlated with a decrease in cell proliferation within 5 h of retinoic acid administration, specifically in the posterior half of the distal limb bud mesenchyme, from which the distal skeletal elements are generated. There is a specific downregulation of Fgf4 , a gene known to be involved in limb bud outgrowth and expressed only in the posterior part of the apical ectodermal ridge; Fgf8 , which is expressed throughout the apical ectodermal ridge, is unaffected. The reduction in Fgf4 expression is not accompanied by downregulation of Shh , nor of its receptor and downstream target gene Ptc , suggesting that the skeletal reduction defects induced by retinoic acid are mediated specifically by FGF4‐induced skeletogenic mesenchymal cell proliferation.