Siegenthaler Julie A, Ashique Amir M, Zarbalis Konstantinos, Patterson Katelin P, Hecht Jonathan H, Kane Maureen A, Folias Alexandra E, Choe Youngshik, May Scott R, Kume Tsutomu, Napoli Joseph L, Peterson Andrew S, Pleasure Samuel J
Department of Neurology, Institute for Regenerative Medicine, University of California San Francisco, San Francisco, CA 94158, USA.
Cell. 2009 Oct 30;139(3):597-609. doi: 10.1016/j.cell.2009.10.004.
Extrinsic signals controlling generation of neocortical neurons during embryonic life have been difficult to identify. In this study we demonstrate that the dorsal forebrain meninges communicate with the adjacent radial glial endfeet and influence cortical development. We took advantage of Foxc1 mutant mice with defects in forebrain meningeal formation. Foxc1 dosage and loss of meninges correlated with a dramatic reduction in both neuron and intermediate progenitor production and elongation of the neuroepithelium. Several types of experiments demonstrate that retinoic acid (RA) is the key component of this secreted activity. In addition, Rdh10- and Raldh2-expressing cells in the dorsal meninges were either reduced or absent in the Foxc1 mutants, and Rdh10 mutants had a cortical phenotype similar to the Foxc1 null mutants. Lastly, in utero RA treatment rescued the cortical phenotype in Foxc1 mutants. These results establish RA as a potent, meningeal-derived cue required for successful corticogenesis.
胚胎期控制新皮层神经元生成的外在信号一直难以确定。在本研究中，我们证明背侧前脑脑膜与相邻的放射状胶质细胞终足相互作用，并影响皮层发育。我们利用了在前脑脑膜形成方面存在缺陷的Foxc1突变小鼠。Foxc1的剂量和脑膜缺失与神经元和中间祖细胞产生的显著减少以及神经上皮的延长相关。多种实验表明，视黄酸（RA）是这种分泌活性的关键成分。此外，背侧脑膜中表达Rdh10和Raldh2的细胞在Foxc1突变体中减少或缺失，并且Rdh10突变体具有与Foxc1基因敲除突变体相似的皮层表型。最后，子宫内RA治疗挽救了Foxc1突变体的皮层表型。这些结果确立了RA是成功进行皮层发生所必需的一种强大的、源自脑膜的信号。
