Related Experiment Video

Updated: Jul 2, 2025

Grafting of Beads into Developing Chicken Embryo Limbs to Identify Signal Transduction Pathways Affecting Gene Expression
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Diverse Fgfr1 signaling pathways and endocytic trafficking regulate early mesoderm development

James F Clark1, Philippe Soriano1

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

Biorxiv : the Preprint Server for Biology
|February 26, 2024
PubMed

Insights

Fibroblast growth factor receptor 1 (FGFR1) canonical signaling is crucial for embryonic development. Non-canonical FGFR1 pathways also regulate mesoderm development through cell adhesion and endocytic trafficking.

Area of Science:

  • Developmental Biology
  • Cell Signaling

Background:

  • The Fibroblast growth factor (FGF) pathway is essential for embryonic development.
  • Activated Fibroblast growth factor receptor 1 (FGFR1) initiates canonical signaling cascades like ERK/MAPK and PI3K/AKT.

Approach:

  • Studied hypomorphic mutations in Fgfr1 that impair canonical signaling but allow embryonic development.
  • Investigated the effects of reduced FGFR1 activity on mesodermal tissues, somitogenesis, and gene expression.
  • Utilized proteomic analysis to identify changes in protein interactions and cellular trafficking.

Key Points:

  • Embryos with hypomorphic Fgfr1 mutations show severe mesodermal defects despite reaching birth.
  • Reduced FGFR1 activity leads to earlier lethality, impaired somitogenesis, and altered gene expression.
  • Genes regulating cell migration, extracellular matrix (ECM) interaction, and phosphoinositol signaling are downregulated.
  • Proteomic analysis revealed altered interactions with endocytic pathway components and changes in endocytic trafficking.

Conclusions:

  • Both canonical and non-canonical FGFR1 pathways are critical for early mesoderm development.
  • Non-canonical pathways involve direct interactions with cell adhesion molecules and regulation of endocytic processes.
Keywords:
FGFcell adhesioncell signalingendocytic traffickingkidney developmentmesoderm development

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