Journal
MECHANISMS OF DEVELOPMENT
Volume 124, Issue 9-10, Pages 657-667Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.mod.2007.07.005
Keywords
PI3K; Erk; ErbB; Xenopus; gastrulation
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Funding
- NICHD NIH HHS [HD43345, R01 HD043345-05, R01 HD043345] Funding Source: Medline
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ErbB signaling regulates cell adhesion and movements during Xenopus gastrulation, but the downstream pathways involved have not been elucidated. In this study, we show that phosphatidylinositol-3 kinase (PI3K) and Erk mitogen-activated protein kinase (MAPK) mediate ErbB signaling to regulate gastrulation. Both PI3K and MAPK function sequentially in mesoderm specification and movements, and ErbB signaling is important only for the late phase activation of these pathways to control cell behaviors. Activation of either PI3K or Erk MAPK rescues gastrulation defects in ErbB4 morphant embryos, and restores convergent extension in the trunk mesoderm as well as coherent cell migration in the head mesoderm. The two signals preferentially regulate different aspects of cell behaviors, with PI3K more efficient in rescuing cell adhesion and spreading and MAPK more effective in stimulating the formation of filopodia. PI3K and MAPK also weakly activate each other, and together they modulate gastrulation movements. Our results reveal that PI3K and Erk MAPK, which have previously been considered as mesodermal inducing signals, also act downstream of ErbB signaling to participate in regulation of gastrulation morphogenesis. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
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