Calloni Giordano W, Glavieux-Pardanaud Corinne, Le Douarin Nicole M, Dupin Elisabeth
Centre National de la Recherche Scientifique, Unité Propre de Recherche 2197, Laboratoire de Développement, Evolution, Plasticité du Système Nerveux, Institut de Neurobiologie Alfred Fessard, 91198 Gif-sur-Yvette, France.
Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19879-84. doi: 10.1073/pnas.0708806104. Epub 2007 Dec 6.
In the vertebrate embryo, the cephalic neural crest cells (CNCCs) produce cells belonging to two main lineages: the neural [including neurons, glial cells of the peripheral nervous system (PNS), and melanocytes] and the mesenchymal (chondrocytes, osteoblasts, smooth muscle cells, and connective tissue cells), whereas the trunk NCCs (TNCCs) in amniotes yield only neural derivatives. Although multipotent cells have previously been evidenced by in vitro clonal analysis, the issue as to whether all of the mesenchymal and neural phenotypes can be derived from a unique NC stem cell has remained elusive. In the present work, we devised culture conditions that led us to identify a highly multipotent NCC endowed with both neural and mesenchymal potentials, which lies upstream of all the other NC progenitors known so far. We found that addition of recombinant Sonic Hedgehog (Shh) increased the number of CNCC progenitors yielding both mesenchymal and neural lineages and promoted the development of such precursors from the TNCC. Shh decreased the neural-restricted precursors without affecting the overall CNCC survival and proliferation. By showing a differential positive effect of Shh on the expression of mesenchymal phenotypes (i.e., chondrocytes and smooth muscle cells) by multipotent CNCCs, these results shed insights on the in vivo requirement of Shh for craniofacial morphogenesis. Together with evolutionary considerations, these data also suggest that the mesenchymal-neural precursor represents the ancestral form of the NC stem cell, which in extinct forms of vertebrates (the ostracoderms) was able to yield both the PNS and superficial skeleton.
在脊椎动物胚胎中，头部神经嵴细胞（CNCCs）产生属于两个主要谱系的细胞：神经谱系（包括神经元、外周神经系统的神经胶质细胞和黑素细胞）和间充质谱系（软骨细胞、成骨细胞、平滑肌细胞和结缔组织细胞），而羊膜动物的躯干神经嵴细胞（TNCCs）仅产生神经衍生物。尽管此前通过体外克隆分析已证实存在多能细胞，但关于所有间充质和神经表型是否都可源自单一的神经嵴干细胞这一问题仍未明确。在本研究中，我们设计了培养条件，从而鉴定出一种具有高度多能性的神经嵴细胞，它兼具神经和间充质潜能，且位于迄今已知的所有其他神经嵴祖细胞的上游。我们发现，添加重组音猬因子（Shh）可增加产生间充质和神经谱系的CNCC祖细胞数量，并促进此类前体细胞从TNCC发育而来。Shh减少了神经限制前体细胞，而不影响CNCC的总体存活和增殖。通过显示Shh对多能CNCCs间充质表型（即软骨细胞和平滑肌细胞）表达的差异性积极作用，这些结果揭示了Shh在体内对颅面形态发生的需求。结合进化方面的考虑，这些数据还表明间充质 - 神经前体细胞代表了神经嵴干细胞的原始形式，在已灭绝的脊椎动物（甲胄鱼）中，它能够产生外周神经系统和表层骨骼。
