Related Experiment Video
Updated: Jun 24, 2025
11:48
Grafting of Beads into Developing Chicken Embryo Limbs to Identify Signal Transduction Pathways Affecting Gene Expression
Published on: January 17, 2016
8.8K
Diverse Fgfr1 signaling pathways and endocytic trafficking regulate mesoderm development
James F Clark1, Philippe Soriano2
1Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
Genes & Development
|June 4, 2024
Summary
Fibroblast growth factor receptor 1 (FGFR1) canonical signaling is crucial for embryonic development. Noncanonical FGFR1 pathways also regulate mesoderm development through cell adhesion and endocytic trafficking.
Area of Science:
- Developmental Biology
- Cell Signaling
Background:
- Fibroblast growth factor (FGF) signaling is essential for embryonic development.
- FGFR1 activates canonical pathways like ERK/MAPK and PI3K/AKT.
Purpose of the Study:
- Investigate the role of canonical and noncanonical FGFR1 signaling in mesoderm development.
- Characterize defects in embryos with hypomorphic FGFR1 mutations.
Main Methods:
- Analysis of embryos with hypomorphic FGFR1 mutations.
- Transcriptional and proteomic analyses.
- Assessment of cellular endocytic trafficking.
Main Results:
- Hypomorphic FGFR1 mutations cause mesodermal defects despite intact canonical signaling.
- Reduced FGFR1 activity leads to earlier lethality and impaired somitogenesis.
- Downregulation of migration, ECM interaction, and phosphoinositol signaling genes observed.
- Proteomics revealed altered interactions with endocytic pathway components.
- Mutant receptor cells exhibit changes in endocytic trafficking.
Conclusions:
- Both canonical and noncanonical FGFR1 pathways are vital for early mesoderm development.
- FGFR1 regulates mesoderm development via cell adhesion and endocytic pathway modulation.
Related Concept Videos
01:15Receptor Downregulation in MVBs
2.0K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.0K
02:33Hedgehog Signaling Pathway
7.3K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.3K
01:41Non-Canonical Wnt Signaling Pathways
7.3K
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
7.3K
03:14Notch Signaling Pathway
4.2K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.2K
01:24Regulation of Angiogenesis and Blood Supply
2.5K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.1K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.1K