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LHX2 Mediates the FGF-to-SHH Regulatory Loop during Limb Development
Billy A Watson1,2, Jennifer M Feenstra3, Jonathan M Van Arsdale4
1Department of Pathology and Human Anatomy, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA. bawatson@llu.edu.
Journal of Developmental Biology
|June 20, 2018
Summary
Fibroblast growth factors (Fgfs) regulate limb development by maintaining Sonic hedgehog (Shh) expression. LHX2 acts as a key intermediate in this crucial FGF-Shh signaling feedback loop.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Fibroblast growth factors (Fgfs) and Sonic hedgehog (Shh) signaling are essential for limb development.
- The feedback loop between Fgf and Shh is critical for patterning but not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying the Fgf-Shh signaling crosstalk during limb development.
- To identify key regulators involved in maintaining Shh expression in response to Fgf signaling.
Main Methods:
- Comparative transcriptome analysis of limb bud cells treated with Fgf beads.
- Identification of candidate genes involved in Shh regulation.
- Functional validation of identified genes, including LHX2.
Main Results:
- Fgf bead implantation induced Shh expression in a dose- and time-dependent manner.
- Comparative analysis identified 25 candidate genes, with eight directly linked to Shh expression or function.
- LHX2 was identified as a crucial intermediate in Fgf-mediated Shh regulation.
Conclusions:
- LHX2 acts as a competency factor, maintaining distal posterior Shh expression under the apical ectodermal ridge.
- This study clarifies a key mechanism in the Fgf-Shh feedback loop essential for limb patterning.
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