FGF-regulated Etv genes are essential for repressing Shh expression in mouse limb buds.

Abstract	Anterior-posterior (A-P) patterning of the vertebrate limb is controlled by sonic hedgehog (SHH) signaling, and the precise restriction of Shh expression to the posterior limb bud is essential for its polarizing effect. Fibroblast growth factor (FGF) signaling, a key control of proximal-distal (P-D) limb outgrowth, is known to promote Shh expression in the posterior limb bud. Here, we show that conditional knockout of the FGF-activated transcription factor genes Etv4 and Etv5 in mouse led to ectopic Shh expression in the anterior limb bud and a preaxial polydactyly (PPD) skeletal phenotype. These unexpected results suggest that ETV4 and ETV5 act downstream of FGF signaling to inhibit Shh expression in the anterior limb bud. This finding elucidates a novel aspect of the mechanism coordinating limb development along the A-P and P-D axes.
Authors	Zhen Zhang, Jamie M Verheyden, John A Hassell, Xin Sun
Journal	Developmental cell (Dev Cell) Vol. 16 Issue 4 Pg. 607-13 (Apr 2009) ISSN: 1878-1551 [Electronic] United States
PMID	19386269 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References	DNA-Binding Proteins Etv4 protein, mouse Etv5 protein, mouse Hedgehog Proteins Proto-Oncogene Proteins c-ets Receptors, Fibroblast Growth Factor Repressor Proteins Shh protein, mouse Transcription Factors Fibroblast Growth Factors Cre recombinase Integrases
Topics	Animals Body Patterning Cell Death DNA-Binding Proteins (chemistry, genetics) Down-Regulation Exons (genetics) Fibroblast Growth Factors (metabolism) Gene Expression Regulation, Developmental HeLa Cells Hedgehog Proteins (metabolism) Humans Integrases (metabolism) Limb Buds (cytology, embryology, metabolism) Mesoderm (cytology, metabolism) Mice Mutation (genetics) Polydactyly (pathology) Proto-Oncogene Proteins c-ets (genetics, metabolism) Receptors, Fibroblast Growth Factor (metabolism) Repressor Proteins (metabolism) Sequence Deletion Signal Transduction Transcription Factors (chemistry, genetics, metabolism)

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