Genetic Requirement of talin1 for Proliferation of Cranial Neural Crest Cells during Palate Development

Background: Craniofacial malformations are among the most common congenital anomalies. Cranial neural crest cells (CNCCs) form craniofacial structures involving multiple cellular processes, perturbations of which contribute to craniofacial malformations. Adhesion of cells to the extracellular matrix mediates bidirectional interactions of the cells with their extracellular environment that plays an important role in craniofacial morphogenesis. Talin (tln) is crucial in cell-matrix adhesion between cells, but its role in craniofacial morphogenesis is poorly understood. Methods: Talin gene expression was determined by whole mount in situ hybridization. Craniofacial cartilage and muscles were analyzed by Alcian blue in Tg(mylz2:mCherry) and by transmission electron microscopy. Pulse-chase photoconversion, 5-ethynyl-2'-deoxyuridine proliferation, migration, and apoptosis assays were performed for functional analysis. Results: Expression of tln1 was observed in the craniofacial cartilage structures, including the palate. The Meckel's cartilage was hypoplastic, the palate was shortened, and the craniofacial muscles were malformed in tln1 mutants. Pulse-chase and EdU assays during palate morphogenesis revealed defects in CNCC proliferation in mutants. No defects were observed in CNCC migration and apoptosis. Conclusions: The work shows that tln1 is critical for craniofacial morphogenesis in zebrafish. Loss of tln1 leads to a shortened palate and Meckel's cartilage along with disorganized skeletal muscles. Investigations into the cellular processes show that tln1 is required for CNCC proliferation during palate morphogenesis. The work will lead to a better understanding of the involvement of cytoskeletal proteins in craniofacial morphogenesis. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Published online 19 March 2018. Received for publication October 31, 2017; accepted November 16, 2017. Presented at the 57th Annual Meeting of New England Society of Plastic and Reconstructive Surgeons, June 11, 2016, Bretton Woods, N.H.; 39th Annual Meeting of Society of Craniofacial Genetics and Developmental Biology, August 4, 2016, Boston, Mass.; 62nd Annual Meeting of Plastic Surgeon Research Council, May 5, 2017, Durham, N.C. Disclosure: The authors have no financial interest to declare in relation to the content of this article. The Article Processing Charge was paid for by the authors. Supplemental digital content is available for this article. Clickable URL citations appear in the text. Drs. Ishii and Mukherjee contributed equally to this work. Eric C. Liao, MD, PhD, Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114., E-mail: cliao@partners.org Copyright © 2018 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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