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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
Summary
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.
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