Dottori M, Gross M K, Labosky P, Goulding M
Molecular Neurobiology Laboratory, The Salk Institute, 10010 North Torrey Pines Rd, La Jolla, CA 92037, USA.
Development. 2001 Nov;128(21):4127-38. doi: 10.1242/dev.128.21.4127.
The neural crest is a migratory cell population that gives rise to multiple cell types in the vertebrate embryo. The intrinsic determinants that segregate neural crest cells from multipotential dorsal progenitors within the neural tube are poorly defined. In this study, we show that the winged helix transcription factor Foxd3 is expressed in both premigratory and migratory neural crest cells. Foxd3 is genetically downstream of Pax3 and is not expressed in regions of Pax3 mutant mice that lack neural crest, implying that Foxd3 may regulate aspects of the neural crest differentiation program. We show that misexpression of Foxd3 in the chick neural tube promotes a neural crest-like phenotype and suppresses interneuron differentiation. Cells that ectopically express Foxd3 upregulate HNK1 and Cad7, delaminate and emigrate from the neural tube at multiple dorsoventral levels. Foxd3 does not induce Slug and RhoB, nor is its ability to promote a neural crest-like phenotype enhanced by co-expression of Slug. Together these results suggest Foxd3 can function independently of Slug and RhoB to promote the development of neural crest cells from neural tube progenitors.
神经嵴是一种迁移性细胞群体，在脊椎动物胚胎中可产生多种细胞类型。在神经管内，将神经嵴细胞与多能背侧祖细胞分离的内在决定因素尚不清楚。在本研究中，我们发现有翼螺旋转录因子Foxd3在迁移前和迁移中的神经嵴细胞中均有表达。Foxd3在基因上位于Pax3下游，在缺乏神经嵴的Pax3突变小鼠区域中不表达，这意味着Foxd3可能调控神经嵴分化程序的某些方面。我们发现，在鸡神经管中过表达Foxd3会促进神经嵴样表型，并抑制中间神经元分化。异位表达Foxd3的细胞会上调HNK1和Cad7，在多个背腹水平从神经管分层并迁出。Foxd3不诱导Slug和RhoB，其促进神经嵴样表型的能力也不会因共表达Slug而增强。这些结果共同表明，Foxd3可独立于Slug和RhoB发挥作用，促进神经管祖细胞发育为神经嵴细胞。
