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Genetic Interactions Between FGF and SHH Signaling in the Vertebrate Limb
Author(s) -
Verheyden Jamie M,
Sun Xin
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a199-d
Subject(s) - limb development , fibroblast growth factor , sonic hedgehog , limb bud , zone of polarizing activity , apical ectodermal ridge , mesenchyme , microbiology and biotechnology , biology , signal transduction , mesenchymal stem cell , endocrinology , medicine , anatomy , genetics , gene , mesoderm , embryonic stem cell , receptor , embryo
Fibroblast Growth Factors (FGFs) have been shown to play a major role in the development of the proximal (shoulder)/distal (fingertip)(P/D) axis in limbs. Development along the P/D axis is the least understood and major questions still remain as to which genes act downstream of FGF signaling to regulate outgrowth of the limb. This work addresses the mechanism of how the FGF signal from the apical ectodermal ridge (AER) of the limb bud directs adjacent mesenchymal cells to form appropriate skeletal elements along the P/D axis. One of the prominent candidate factors that may mediate FGF function is Sonic Hedgehog (SHH). Previous studies show that Shh expression in the limb bud mesenchyme is dependent on FGF signaling from the AER. Furthermore, Shh null mutants exhibit reduction of skeletal elements along the P/D axis, suggesting Shh plays a role in P/D development. SHH may mediate AER‐FGF signaling by regulating Fgf expression or by regulating other mesenchymal targets downstream of AER‐FGF signaling. This study investigates the genetic interactions between Fgf and Shh mutants in mouse in order to address the mechanism of how FGF and SHH signaling function together in limb P/D development. Supported by NICHD RO1 awarded to Xin Sun