Present address: University Medical School of Geneva, Department of Physiology and Metabolism, Rue Michel Servet, CH-1211 Geneva.
Injury-induced activation of the MAPK/CREB pathway triggers apoptosis-induced compensatory proliferation in hydra head regeneration
Article first published online: 22 FEB 2011
© 2011 The Authors. Journal compilation © 2011 Japanese Society of Developmental Biologists
Development, Growth & Differentiation
Volume 53, Issue 2, pages 186–201, February 2011
How to Cite
Chera, S., Ghila, L., Wenger, Y. and Galliot, B. (2011), Injury-induced activation of the MAPK/CREB pathway triggers apoptosis-induced compensatory proliferation in hydra head regeneration. Development, Growth & Differentiation, 53: 186–201. doi: 10.1111/j.1440-169X.2011.01250.x
- Issue published online: 22 FEB 2011
- Article first published online: 22 FEB 2011
- Received 9 September 2010; revised 23 December 2010; accepted 24 December 2010.
- apoptosis-induced compensatory proliferation;
- CREB binding protein;
- hydra regeneration;
- injury-induced apoptosis;
- MAPK/ERK/CREB pathway;
- Ribosomal S6 kinase
After bisection, Hydra polyps regenerate their head from the lower half thanks to a head-organizer activity that is rapidly established at the tip. Head regeneration is also highly plastic as both the wild-type and the epithelial Hydra (that lack the interstitial cell lineage) can regenerate their head. In the wild-type context, we previously showed that after mid-gastric bisection, a large subset of the interstitial cells undergo apoptosis, inducing compensatory proliferation of the surrounding progenitors. This asymmetric process is necessary and sufficient to launch head regeneration. The apoptotic cells transiently release Wnt3, which promotes the formation of a proliferative zone by activating the beta-catenin pathway in the adjacent cycling cells. However the injury-induced signaling that triggers apoptosis is unknown. We previously reported an asymmetric immediate activation of the mitogen-activated protein kinase/ribosomal S6 kinase/cAMP response element binding protein (MAPK/RSK/CREB) pathway in head-regenerating tips after mid-gastric bisection. We show here that pharmacological inhibition of the MAPK/ERK pathway or RNAi knockdown of the RSK, CREB, CREB binding protein (CBP) genes prevents apoptosis, compensatory proliferation and blocks head regeneration. As the activation of the MAPK pathway upon injury plays an essential role in regenerating bilaterian species, these results suggest that the MAPK-dependent activation of apoptosis-induced compensatory proliferation represents an evolutionary-conserved mechanism to launch a regenerative process.