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.
['Haupaix|Nicolas|N|', 'Stolfi|Alberto|A|', 'Sirour|Cathy|C|', 'Picco|Vincent|V|', 'Levine|Michael|M|', 'Christiaen|Lionel|L|', 'Yasuo|Hitoyoshi|H|']
D000818:Animals D015153:Blotting, Western D002454:Cell Differentiation D019070:Cell Lineage D002938:Ciona intestinalis D017931:DNA Primers D018274:Electroporation D004625:Embryo, Nonmammalian D005346:Fibroblast Growth Factors D007150:Immunohistochemistry D017403:In Situ Hybridization D020935:MAP Kinase Signaling System D020729:p120 GTPase Activating Protein
p120RasGAP Ephrin Ascidian Ciona intestinalis