Carney Rosalind S E, Cocas Laura A, Hirata Tsutomu, Mansfield Kevin, Corbin Joshua G
Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010, USA.
Cereb Cortex. 2009 Apr;19(4):745-59. doi: 10.1093/cercor/bhn123. Epub 2008 Aug 12.
In the embryonic telencephalon, the pallial-subpallial boundary (PSB) separates the dorsal Pax6+ pallium from the ventral Gsh2+ subpallium. Previous studies have revealed that this region is a source of cells that will populate both the olfactory bulb and basal telencephalic limbic system. However, the level of progenitor cell heterogeneity and developmental genetic regulation of this progenitor region remains to be fully elucidated. In this study we carried out a comprehensive analysis of gene expression patterns at the PSB, in addition to an examination of the combinatorial function of Pax6 and Gsh2 in the specification of the PSB. First, we reveal that the PSB is comprised of a complex mix of molecularly distinct progenitor pools. In addition, by analysis of single Sey, Gsh2, and Sey/Gsh2 double mutant mice, we demonstrate that both Pax6 and Gsh2 are directly required for major aspects of PSB progenitor specification. Our analysis also reveals that the establishment of the epidermal growth factor receptor positive lateral cortical stream migratory route to the basal telencephalon is Pax6 dependent. Thus, in addition to their well-characterized cross-repressive roles in dorsal/ventral patterning our analyses reveal important novel functions of Gsh2 and Pax6 in the regulation of PSB progenitor pool specification and patterning.
在胚胎端脑中,皮质 - 皮质下边界(PSB)将背侧Pax6 +皮质与腹侧Gsh2 +皮质下区分开。先前的研究表明,该区域是细胞的来源,这些细胞将填充嗅球和基底端脑边缘系统。然而,该祖细胞区域的祖细胞异质性水平和发育遗传调控仍有待充分阐明。在本研究中,我们除了研究Pax6和Gsh2在PSB特化中的组合功能外,还对PSB处的基因表达模式进行了全面分析。首先,我们发现PSB由分子上不同的祖细胞群的复杂混合物组成。此外,通过对单只Sey、Gsh2以及Sey / Gsh2双突变小鼠的分析,我们证明Pax6和Gsh2都是PSB祖细胞特化主要方面的直接必需因素。我们的分析还表明,表皮生长因子受体阳性的外侧皮质流向基底端脑的迁移途径的建立依赖于Pax6。因此,除了它们在背腹模式形成中已被充分表征的相互抑制作用外,我们的分析还揭示了Gsh2和Pax6在调节PSB祖细胞群特化和模式形成中的重要新功能。