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The PDGF alpha receptor is required for neural crest cell development and for normal patterning of the somites
1Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. psoriano@fhcrc.org
Abstract:
Platelet-derived growth factors (PDGFs) have been implicated in the control of cell proliferation, survival and migration. Patch mutant mice harbor a deletion including the PDGF alpha receptor gene and exhibit defects of neural crest origin which affect pigmentation in heterozygotes and cranial bones in homozygotes. To verify the role of the PDGF alphaR gene during development, mice carrying a targeted null mutation were generated. No pigmentation phenotype was observed in heterozygotes. Homozygotes die during embryonic development and exhibit incomplete cephalic closure similar to that observed in a subset of Patch mutants. In addition, increased apoptosis was observed on pathways followed by migrating neural crest cells. However, alterations in mutant vertebrae, ribs and sternum were also observed, which appear to stem from a deficiency in myotome formation. These results indicate that PDGFs may exert their functions during early embryogenesis by affecting cell survival and patterning.
Insights
Platelet-derived growth factors (PDGFs) are crucial for embryonic development. PDGF alpha receptor null mutations cause embryonic lethality and defects in neural crest cell migration and myotome formation.
Area of Science:
- Developmental Biology
- Genetics
- Cell Biology
Background:
- Platelet-derived growth factors (PDGFs) regulate cell proliferation, survival, and migration.
- Patch mutant mice, lacking PDGF alpha receptor (PDGF alphaR), show developmental defects.
Purpose of the Study:
- To investigate the role of the PDGF alphaR gene in embryonic development using a targeted null mutation.
- To clarify the specific developmental processes influenced by PDGF alphaR signaling.
Main Methods:
- Generation of mice with a targeted null mutation in the PDGF alphaR gene.
- Phenotypic analysis of heterozygotes and homozygotes during embryonic development.
- Assessment of neural crest cell migration and apoptosis.
Main Results:
- PDGF alphaR heterozygotes showed no pigmentation defects.
- Homozygotes exhibited embryonic lethality with incomplete cephalic closure and increased apoptosis in neural crest cell pathways.
- Mutant embryos displayed skeletal abnormalities in vertebrae, ribs, and sternum due to deficient myotome formation.
Conclusions:
- PDGF alphaR signaling is essential for embryonic development, particularly for neural crest cell survival and migration.
- PDGFs play a critical role in early embryogenesis, influencing cell survival, patterning, and skeletal development.