title: FGF signal interpretation is directed by Sprouty and Spred proteins during mesoderm formation.
abstract: Vertebrate gastrulation requires coordination of mesoderm specification with morphogenetic movements. While both of these processes require FGF signaling, it is not known how mesoderm specification and cell movements are coordinated during gastrulation. The related Sprouty and Spred protein families are recently discovered regulators of receptor tyrosine kinase signaling. We identified two genes for each family in Xenopus tropicalis: Xtsprouty1, Xtsprouty2, Xtspred1, and Xtspred2. In gain- and loss-of-function experiments we show that XtSprouty and XtSpred proteins modulate different signaling pathways downstream of the FGF receptor (FGFR), and consequently different developmental processes. Notably, XtSproutys inhibit morphogenesis and Ca(2+) and PKCdelta signaling, leaving MAPK activation and mesoderm specification intact. In contrast, XtSpreds inhibit MAPK activation and mesoderm specification, with little effect on Ca(2+) or PKCdelta signaling. These differences, combined with the timing of their developmental expression, suggest a mechanism to switch FGFR signal interpretation to coordinate mesoderm formation and cell movements during gastrulation.
authors.affiliation: The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Sivak
authors.forename: Lars F
authors.initials: LF
authors.lastname: Petersen
authors.forename: Enrique
authors.initials: E
authors.lastname: Amaya
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D020013:Calcium Signaling; D002465:Cell Movement; D005346:Fibroblast Growth Factors / Q000502:physiology*; D005775:Gastrula / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D008648:Mesoderm / Q000166:cytology* / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D051745:Protein Kinase C-delta; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D014981:Xenopus / Q000196:embryology* / Q000235:genetics / Q000502:physiology*; D029867:Xenopus Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D008565:Membrane Proteins; D010750:Phosphoproteins; D017468:Receptors, Fibroblast Growth Factor; D012097:Repressor Proteins; D029867:Xenopus Proteins; D005346:Fibroblast Growth Factors; D011493:Protein Kinase C; D051745:Protein Kinase C-delta