p120RasGAP mediates ephrin/Eph-dependent attenuation of FGF/ERK signals during cell fate specification in ascidian embryos.
ERK1/2 MAP kinase exhibits a highly dynamic activation pattern in developing embryos, which largely depends on fibroblast growth factor (FGF) signals. In ascidian embryos, FGF-dependent activation of ERK1/2 occurs differentially between sister cells during marginal zone and neural lineage patterning. Selective attenuation of FGF signals by localised ephrin/Eph signals accounts for this differential ERK activation, which controls the binary fate choice of each sibling cell pair. Here, we show that p120 Ras GTPase-activating protein (p120RasGAP) is a crucial mediator of these ephrin/Eph signals. First, inhibition of p120RasGAP has a similar effect to inhibition of ephrin/Eph function during marginal zone and neural patterning. Second, p120RasGAP acts epistatically to ephrin/Eph signals. Third, p120RasGAP physically associates with Eph3 in an ephrin-dependent manner. This study provides the first in vivo evidence that the functional association between Eph and RasGAP controls the spatial extent of FGF-activated ERK.
Université Pierre et Marie Curie and Centre National de la Recherche Scientifique, Laboratoire de Biologie du Développement de Villefranche-sur-Mer, Observatoire Océanologique, 06230 Villefranche-sur-Mer, France.
Nicolas
N
Haupaix
Alberto
A
Stolfi
Cathy
C
Sirour
Vincent
V
Picco
Michael
M
Levine
Lionel
L
Christiaen
Hitoyoshi
H
Yasuo
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D002938:Ciona intestinalis / Q000196:embryology*; D017931:DNA Primers / Q000235:genetics; D018274:Electroporation; D004625:Embryo, Nonmammalian / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020729:p120 GTPase Activating Protein / Q000378:metabolism*
D017931:DNA Primers; D020729:p120 GTPase Activating Protein; D005346:Fibroblast Growth Factors
Ascidian; Ciona intestinalis; Ephrin; p120RasGAP