Development · 1997 · 715 citations · 42 references
Life SciencesDevelopmental BiologyGeneticsCraniofacial DevelopmentEmbryogenesisMorphogenesisCraniofacial Developmental GeneticsHead DevelopmentNeural Crest DevelopmentNeural Crest GeneticsNeural DevelopmentSkeletal DevelopmentCephalic StructuresCranial Neural Crest Cell DevelopmentCranial Neural Crest CellsEmbryonic Development GeneticsNeural Crest Cell ProliferationNeural Crest DerivativesNeural Crest MorphogenesisNeural Crest Proliferation
Platelet‑derived growth factors regulate cell proliferation, survival, and migration, and loss of the PDGFα receptor in Patch mutant mice causes neural‑crest‑derived pigmentation and cranial bone defects. The study aimed to determine the developmental role of the PDGFα receptor. This was addressed by generating mice with a targeted null mutation of the PDGFαR gene. Homozygous mutants died embryonically with incomplete cephalic closure, increased apoptosis along neural‑crest pathways, and skeletal defects from impaired myotome formation, while heterozygotes showed no pigmentation phenotype, indicating that PDGFα signaling is essential for early embryonic cell survival and patterning.
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 PDGFα 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 PDGFαR 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.
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Per Levéen, Milos Pekny, Samuel Gebré‐Medhin et al. · Genes & Development · 1994 · 1.1K citations · Full text