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Updated: Apr 20, 2026

Isolation of Whole Cell Protein Lysates from Mouse Facial Processes and Cultured Palatal Mesenchyme Cells for Phosphoprotein Analysis
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Isolation of Whole Cell Protein Lysates from Mouse Facial Processes and Cultured Palatal Mesenchyme Cells for Phosphoprotein Analysis

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SRF regulates craniofacial development through selective recruitment of MRTF cofactors by PDGF signaling

Harish N Vasudevan1, Philippe Soriano1

  • 1Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Developmental Cell
|December 3, 2014
PubMed

Insights

Serum response factor (SRF) is crucial for craniofacial development, regulating cell proliferation and migration. PDGF signaling specifically activates SRF-dependent genes, revealing a mechanism for receptor tyrosine kinase specificity.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Receptor tyrosine kinase (RTK) signaling pathways, including platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF), are essential for mammalian craniofacial development.
  • The specific downstream transcriptional regulators mediating these developmental processes are not fully understood.

Purpose of the Study:

  • To investigate the role of serum response factor (SRF) as a downstream transcriptional effector in RTK signaling during craniofacial development.
  • To elucidate the mechanism by which PDGF and FGF signaling pathways exert specificity in craniofacial development.

Main Methods:

  • Utilized mouse embryonic palatal mesenchyme cells to study SRF induction by PDGF and FGF.
  • Generated Srf neural crest conditional mutants to assess craniofacial phenotypes.
  • Performed genetic interaction studies between Srf and Pdgfra or Fgfr1 mutants.
  • Employed ChIP-seq to analyze genome-wide SRF binding.
  • Investigated cofactor activation (MRTF-dependent) in response to signaling pathways.

Main Results:

  • SRF is induced by both PDGF and FGF signaling in palatal mesenchyme cells.
  • Srf neural crest conditional mutants display facial clefting, with associated defects in cell proliferation and migration.
  • Genetic interactions indicate Srf and Pdgfra, but not Srf and Fgfr1, are functionally linked in craniofacial development.
  • PDGF selectively activates a network of MRTF-dependent cytoskeletal genes, demonstrating differential cofactor usage and signal specificity.

Conclusions:

  • SRF plays a critical role in regulating cell proliferation and migration during mammalian craniofacial development.
  • Differential cofactor usage by SRF mediates signal specificity between PDGF and FGF pathways.
  • A PDGF-responsive, SRF-driven transcriptional program is identified in the midface, highlighting a novel mechanism in craniofacial development.

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