FGF signaling regulates mesoderm cell fate specification and morphogenetic movement at the primitive streak.
Although FGF signaling plays an integral role in the migration and patterning of mesoderm at gastrulation, the mechanism and downstream targets of FGF activity have remained elusive. Here, we demonstrate that FGFR1 orchestrates the epithelial to mesenchymal transition and morphogenesis of mesoderm at the primitive streak by controlling Snail and E-cadherin expression. Furthermore, we show that FGFR1 functions in mesoderm cell fate specification by positively regulating Brachyury and Tbx6 expression. Finally, we provide evidence that the attenuation of Wnt3a signaling observed in Fgfr1 -/- embryos can be rescued by lowering E-cadherin levels. We propose that modulation of cytoplasmic beta-catenin levels, associated with FGF-induced downregulation of E-cadherin, provides a molecular link between FGF and Wnt signaling pathways at the streak.
Ciruna
B
B
Department of Molecular and Medical Genetics, University of Toronto, Ontario, Canada.
Rossant
J
J
D000818:Animals; D015820:Cadherins / Q000235:genetics; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005326:Fetal Proteins; D005775:Gastrula / Q000166:cytology / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D008297:Male; D008648:Mesoderm / Q000166:cytology / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D008817:Mice, Mutant Strains; D009154:Mutation / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D000071250:Snail Family Transcription Factors; D020825:T-Box Domain Proteins / Q000235:genetics; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D000098908:Brachyury Protein
D015820:Cadherins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D005326:Fetal Proteins; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor; D000071250:Snail Family Transcription Factors; D020825:T-Box Domain Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D000098908:Brachyury Protein; C495267:CTNNB1 protein, mouse; C102932:Tbx6 protein, mouse; C491180:tbx6 protein, zebrafish; C496349:Fgfr1 protein, mouse