Journal
DEVELOPMENTAL CELL
Volume 20, Issue 5, Pages 689-699Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2011.04.010
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Funding
- NIH [MH083804]
- Feinberg
- Sinsheimer
- McDonnell Foundations
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Growing evidence suggests that FGFs secreted from embryonic signaling centers are key mediators of cell survival. However, the mechanisms regulating FGF-dependent cell survival remain obscure. At the rostral end of the embryo, for example, ablation of FGF signaling leads to the rapid death of the precursor cells that form the anterior head, including the telencephalon. Here, we outline a core genetic circuit that regulates survival in the embryonic mouse head: WNT signaling through beta-catenin directly maintains FGF expression and requires FGF function in vivo to oppose proapoptotic TGF-beta signaling through SMAD4. Moreover, these antagonistic pathways converge on the transcriptional regulation of apoptosis, and genes such as Cdkn1a, suggesting a mechanism for how signaling centers in the embryonic head regulate cell survival.
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