1. LKB1 signaling in cephalic neural crest cells is essential for vertebrate head development.
- Author
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Creuzet SE, Viallet JP, Ghawitian M, Torch S, Thélu J, Alrajeh M, Radu AG, Bouvard D, Costagliola F, Borgne ML, Buchet-Poyau K, Aznar N, Buschlen S, Hosoya H, Thibert C, and Billaud M
- Subjects
- AMP-Activated Protein Kinases physiology, Animals, Avian Proteins antagonists & inhibitors, Avian Proteins genetics, Chick Embryo, Craniofacial Abnormalities embryology, Craniofacial Abnormalities genetics, Gene Expression Regulation, Developmental, Gene Silencing, Head embryology, Mice, Mice, Knockout, Myosin Light Chains physiology, Neural Crest cytology, Protein Serine-Threonine Kinases antagonists & inhibitors, Protein Serine-Threonine Kinases deficiency, Protein Serine-Threonine Kinases genetics, Signal Transduction genetics, Signal Transduction physiology, rho-Associated Kinases physiology, Avian Proteins physiology, Neural Crest physiology, Protein Serine-Threonine Kinases physiology
- 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., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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