FGF Signal Interpretation Is Directed by Sprouty and Spred Proteins during Mesoderm Formation

J. M. Sivak, L. F. Petersen and E. Amaya

Developmental Cell 8:689-701 (2005) (Full Article, 800 Kb)

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 Ca2+ and PKCδ signaling, leaving MAPK activation a

nd mesoderm specification intact. In contrast, XtSpreds inhibit MAPK activation and mesoderm specification, with little effect on Ca2+

or PKCδ 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.

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