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LKB1 signaling in cephalic neural crest cells is essential for vertebrate head development

Author:
Creuzet, Sophie E., Viallet, Jean P., Ghawitian, Maya, Torch, Sakina, Thélu, Jacques, Alrajeh, Moussab, Radu, Anca G., Bouvard, Daniel, Costagliola, Floriane, Borgne, Maïlys Le, Buchet-Poyau, Karine, Aznar, Nicolas, Buschlen, Sylvie, Hosoya, Hiroshi, Thibert, Chantal, Billaud, Marc
Source:
Developmental biology 2016 v.418 pp. 283-296
ISSN:
0012-1606
Subject:
AMP-activated protein kinase, brain, delamination, head, myosin, neural crest, skeleton, vertebrates
Abstract:
Head development in vertebrates proceeds through a series of elaborate patterning mechanisms and cell-cell interactions involving cephalic neural crest cells (CNCC). These cells undergo extensive migration along stereotypical paths after their separation from the dorsal margins of the neural tube and they give rise to most of the craniofacial skeleton. Here, we report that the silencing of the LKB1 tumor suppressor affects the delamination of pre-migratory CNCC from the neural primordium as well as their polarization and survival, thus resulting in severe facial and brain defects. We further show that LKB1-mediated effects on the development of CNCC involve the sequential activation of the AMP-activated protein kinase (AMPK), the Rho-dependent kinase (ROCK) and the actin-based motor protein myosin II. Collectively, these results establish that the complex morphogenetic processes governing head formation critically depends on the activation of the LKB1 signaling network in CNCC.
Agid:
5564031