Related Experiment Video

Updated: May 22, 2025

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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Downstream branches of receptor tyrosine kinase signaling act interdependently to shape the face

Nicholas Hanne1, Diane Hu1, Marta Vidal-García2

  • 1Department of Orthopaedic Surgery, University of California-San Francisco, San Francisco, California, USA.

Developmental Dynamics : an Official Publication of the American Association of Anatomists
|May 20, 2025
PubMed
Abstract

Insights

Investigating fibroblast growth factor (FGF) signaling in chicken embryos revealed that inhibiting downstream pathways like MEK1/2, PI3K, and PLCγ disrupts craniofacial development. These pathways appear robust due to developmental redundancy.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Craniofacial Development

Background:

  • Fibroblast growth factor (FGF) signaling impacts neural crest cell development in the embryonic frontonasal process (FNP).
  • Previous work linked increased FGF signaling to FNP dysmorphology, reduced proliferation, and altered cell orientation, with specific MAPK pathway involvement.

Purpose of the Study:

  • To investigate the roles of three downstream branches of receptor tyrosine kinase (RTK) signaling: MEK1/2, PI3K, and PLCγ.
  • To determine how inhibiting these pathways affects cellular activities and FNP morphogenesis.

Main Methods:

  • Small molecule inhibitors targeting MEK1/2, PI3K, and PLCγ were applied to the chicken embryo FNP.
  • Treatments were administered individually and in combination.
  • Effects on proliferation, cellular orientation, apoptosis, and overall FNP morphology were assessed.

Main Results:

  • Inhibition of MEK1/2, PI3K, or PLCγ individually or together resulted in asymmetric proximodistal truncation of the treated FNP.
  • All treatments led to decreased cell proliferation and disrupted cellular orientation.
  • A mild increase in apoptosis was observed, but the primary effects were on growth and cell arrangement.

Conclusions:

  • Downstream RTK signaling pathways are resilient to developmental disruption.
  • Redundant signaling systems likely contribute to the robustness of craniofacial development despite perturbations.
Keywords:
cellular activitycraniofacialmorphogenesistyrosine kinase signaling

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