Carney Rosalind S E, Alfonso Teresa B, Cohen Daniela, Dai Haining, Nery Susana, Stoica Bogdan, Slotkin Jonathan, Bregman Barbara S, Fishell Gord, Corbin Joshua G
Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.
J Neurosci. 2006 Nov 8;26(45):11562-74. doi: 10.1523/JNEUROSCI.3092-06.2006.
During embryogenesis, the lateral cortical stream (LCS) emerges from the corticostriatal border (CSB), the boundary between the developing cerebral cortex and striatum. The LCS is comprised of a mix of pallial- and subpallial-derived neural progenitor cells that migrate to the developing structures of the basal telencephalon, most notably the piriform cortex and amygdala. Using a combination of in vitro and in vivo approaches, we analyzed the timing, composition, migratory modes, origin, and requirement of the homeodomain-containing transcription factor Gsh2 (genomic screened homeobox 2) in the development of this prominent migratory stream. We reveal that Pax6 (paired box gene 6)-positive pallial-derived and Dlx2 (distal-less homeobox 2)-positive subpallial-derived subpopulations of LCS cells are generated in distinct temporal windows during embryogenesis. Furthermore, our data indicate the CSB border not only is comprised of separate populations of pallial- and subpallial-derived progenitors that contribute to the LCS but also a subpopulation of cells coexpressing Pax6 and Dlx2. Moreover, despite migrating along a route outlined by a cascade of radial glia, the Dlx2-positive population appears to migrate primarily in an apparent chain-like manner, with LCS migratory cells being generated locally at the CSB with little contribution from other subpallial structures such as the medial, lateral, or caudal ganglionic eminences. We further demonstrate that the generation of the LCS is dependent on the homeodomain-containing gene Gsh2, revealing a novel requirement for Gsh2 in telencephalic development.
在胚胎发生过程中,外侧皮质流(LCS)起源于皮质纹状体边界(CSB),即发育中的大脑皮质与纹状体之间的边界。LCS由源自皮质和皮质下的神经祖细胞混合组成,这些细胞迁移至基底前脑的发育结构,最显著的是梨状皮质和杏仁核。我们结合体外和体内方法,分析了含同源结构域的转录因子Gsh2(基因组筛选同源框2)在这一重要迁移流发育过程中的时间、组成、迁移模式、起源和需求。我们发现,LCS细胞中Pax6(配对盒基因6)阳性的源自皮质的亚群和Dlx2(远端缺失同源框2)阳性的源自皮质下的亚群在胚胎发生的不同时间窗口产生。此外,我们的数据表明,CSB边界不仅由分别对LCS有贡献的源自皮质和皮质下的祖细胞群体组成,还包括共表达Pax6和Dlx2的细胞亚群。而且,尽管Dlx2阳性群体沿着由一系列放射状胶质细胞勾勒出的路径迁移,但它似乎主要以明显的链状方式迁移,LCS迁移细胞在CSB局部产生,来自其他皮质下结构(如内侧、外侧或尾侧神经节隆起)的贡献很小。我们进一步证明,LCS的产生依赖于含同源结构域的基因Gsh2,揭示了Gsh2在端脑发育中的新需求。