Fgf-dependent Etv4/5 activity is required for posterior restriction of Sonic Hedgehog and promoting outgrowth of the vertebrate limb

Junhao Mao, Edwina McGlinn, Peng Huang, Clifford Tabin, Andrew McMahon

Research output: Contribution to journalArticleResearchpeer-review

106 Citations (Scopus)

Abstract

Crosstalk between the fibroblast growth factor (FGF) and Sonic Hedgehog (Shh) pathways is critical for proper patterning and growth of the developing limb bud. Here, we show that FGF-dependent activation of the ETS transcription factors Etv4 and Etv5 contributes to proximal-distal limb outgrowth. Surprisingly, blockage of Etv activity in early distal mesenchyme also resulted in ectopic, anterior expansion of Shh, leading to a polydactylous phenotype. These data indicate an unexpected function for an FGF/Etv pathway in anterior-posterior patterning. FGF activity in the limb is not only responsible for maintaining posterior-specific Shh expression, but it also acts via Etvs to prevent inappropriate anterior expansion of Shh. This study identifies another level of genetic interaction between the orthogonal axes during limb development.
Original languageEnglish
Pages (from-to)600 - 606
Number of pages7
JournalDevelopmental Cell
Volume16
Issue number4
DOIs
Publication statusPublished - 2009
Externally publishedYes

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