dbx1-expressing cells are necessary for the survival of the mammalian anterior neural and craniofacial structuresdbx1-expressing细胞是哺乳动物的生存所必需的前神经和颅面结构.pdf

Dbx1-Expressing Cells Are Necessary for the Survival of the Mammalian Anterior Neural and Craniofacial Structures ´ ´ 1 1¤ 1 2 2 Frederic Causeret , Monica Ensini , Anne Teissier , Nicoletta Kessaris , William D. Richardson , Thibaut 1 1 Lucas de Couville , Alessandra Pierani * ´ 1 CNRS UMR 7592, Institut Jacques Monod, Univ Paris Diderot, Sorbonne Paris Cite, Paris, France, 2 Department of Cell and Developmental Biology and Wolfson Institute for Biomedical Research, University College London, London, United Kingdom 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,