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Dbx1-Expressing Cells Are Necessary for the Survival of the Mammalian Anterior Neural and Craniofacial Structures

Causeret, F; Ensini, M; Teissier, A; Kessaris, N; Richardson, WD; de Couville, TL; Pierani, A; (2011) Dbx1-Expressing Cells Are Necessary for the Survival of the Mammalian Anterior Neural and Craniofacial Structures. PLOS ONE , 6 (4) , Article e19367. 10.1371/journal.pone.0019367. Green open access

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Abstract

Development of the vertebrate forebrain and craniofacial structures are intimately linked processes, the coordinated growth of these tissues being required to ensure normal head formation. In this study, we identify five small subsets of progenitors expressing the transcription factor dbx1 in the cephalic region of developing mouse embryos at E8.5. Using genetic tracing we show that dbx1-expressing cells and their progeny have a modest contribution to the forebrain and face tissues. However, their genetic ablation triggers extensive and non cell-autonomous apoptosis as well as a decrease in proliferation in surrounding tissues, resulting in the progressive loss of most of the forebrain and frontonasal structures. Targeted ablation of the different subsets reveals that the very first dbx1-expressing progenitors are critically required for the survival of anterior neural tissues, the production and/or migration of cephalic neural crest cells and, ultimately, forebrain formation. In addition, we find that the other subsets, generated at slightly later stages, each play a specific function during head development and that their coordinated activity is required for accurate craniofacial morphogenesis. Our results demonstrate that dbx1-expressing cells have a unique function during head development, notably by controlling cell survival in a non cell-autonomous manner.

Type: Article
Title: Dbx1-Expressing Cells Are Necessary for the Survival of the Mammalian Anterior Neural and Craniofacial Structures
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0019367
Publisher version: http://dx.doi.org/10.1371/journal.pone.0019367
Language: English
Additional information: © 2011 Causeret et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. FC was supported by a Junior/INSERM (Institut National de la Santé et de la Recherche Médicale) contract. ME was supported by the European Commission through STREP contract number 005139 (INTERDEVO). AT was the recipient of fellowships from the French Ministry of Education. AP is a CNRS (Centre National de la Recherche Scientifique) Investigator. This work was supported by grants from the Association pour la Recherche sur le Cancer (ARC) (grant # 4940), Agence Nationale de la Recherche (ANR-07-NEURO-046-01), Fondation pour le Recherche Médicale (INE20060306503), and Ville de Paris (2006 ASES 102) to AP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: BRAIN-DEVELOPMENT, MOUSE EMBRYOS, SPINAL-CORD, CREST, FOREBRAIN, GENE, MORPHOGENESIS, EXPRESSION, MALFORMATION, RECOMBINASE
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research
URI: https://discovery.ucl.ac.uk/id/eprint/1307713
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