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Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
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Receptor tyrosine kinases modulate distinct transcriptional programs by differential usage of intracellular pathways

Harish N Vasudevan1, Pierre Mazot1, Fenglei He1

  • 1Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, United States.

Elife
|May 8, 2015
PubMed

Insights

Platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) signaling have distinct roles in craniofacial development. FGF signaling is MEK-dependent and promotes proliferation, while PDGF signaling is PI3K-dependent and favors differentiation.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cell Signaling

Background:

  • Receptor tyrosine kinases (RTKs) mediate distinct cellular outcomes despite shared signaling pathways.
  • Understanding RTK specificity is crucial for deciphering developmental processes.

Purpose of the Study:

  • To investigate the mechanisms of RTK specificity in craniofacial development.
  • To delineate the transcriptional response to PDGF and FGF signaling in mouse palatal mesenchyme cells.

Main Methods:

  • RNA sequencing (RNA-seq) to analyze gene expression.
  • Inhibition of MEK (Mitogen/Extracellular signal-regulated kinase) and PI3K (phosphoinositide-3-kinase) pathways.
  • In vivo studies in mouse models.

Main Results:

  • Early transcriptional responses to PDGF and FGF are similar, but late responses diverge.
  • FGF signaling is MEK-dependent and promotes cell proliferation.
  • PDGF signaling is PI3K-dependent and promotes cell differentiation, specifically osteoblast differentiation in vivo.

Conclusions:

  • Distinct intracellular pathways (MEK vs. PI3K) mediate specific cellular outcomes for FGF and PDGF.
  • PDGF and FGF signaling pathways exhibit specificity in craniofacial development.
  • The identified differentiation circuit is conserved in vivo, providing insight into RTK specificity mechanisms.
Keywords:
FGFPDGFRTKcomputational biologycraniofacial developmentdevelopmental biologymousestem cellssystems biologytranscription

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