Corbin Joshua G, Rutlin Michael, Gaiano Nicholas, Fishell Gord
Developmental Genetics Program and the Department of Cell Biology, The Skirball Institute of Biomolecular Medicine, New York University Medical Center, 540 First Avenue, New York, NY 10016, USA.
Development. 2003 Oct;130(20):4895-906. doi: 10.1242/dev.00717. Epub 2003 Aug 20.
Regional patterning of the mammalian telencephalon requires the function of three homeodomain-containing transcription factors, Pax6, Gsh2 and Nkx2.1. These factors are required for the development of the dorsal, lateral and medial domains of the telencephalon, respectively. Previous work has indicated that two of the genes encoding these factors, Pax6 and Gsh2, cross-repress one another in the formation of the border between dorsal and lateral region of the telencephalon. Here, we examine whether similar interactions are responsible for the establishment of other boundaries of telencephalic gene expression. Surprisingly, despite the fact that, at specific times in development, both Pax6 and Gsh2 maintain a complementary pattern of expression with Nkx2.1, in neither case are these boundaries maintained through a similar cross-repressive mechanism. Rather, as revealed by analysis of double-mutant mice, Nkx2.1 and Gsh2 act cooperatively in many aspects to pattern the ventral telencephalon. By contrast, as indicated by both loss- and gain-of-function analysis, Gsh2 expression in the medial ganglionic eminence after E10.5 may negatively regulate Nkx2.1 dependent specification of oligodendrocytes. Therefore, both integrative and antagonistic interactions between homeodomain-containing transcription factors contribute to the patterning of the telencephalon.
哺乳动物端脑的区域模式形成需要三种含同源结构域的转录因子Pax6、Gsh2和Nkx2.1发挥作用。这些因子分别是端脑背侧、外侧和内侧区域发育所必需的。先前的研究表明，编码这些因子的两个基因Pax6和Gsh2在端脑背侧和外侧区域边界的形成过程中相互交叉抑制。在此，我们研究类似的相互作用是否负责端脑基因表达其他边界的建立。令人惊讶的是，尽管在发育的特定时期，Pax6和Gsh2与Nkx2.1都保持互补的表达模式，但在这两种情况下，这些边界都不是通过类似的交叉抑制机制维持的。相反，通过对双突变小鼠的分析发现，Nkx2.1和Gsh2在许多方面协同作用，以形成腹侧端脑的模式。相比之下，功能丧失和功能获得分析均表明，E10.5后内侧神经节隆起中Gsh2的表达可能会负向调节Nkx2.1依赖性少突胶质细胞的特化。因此，含同源结构域的转录因子之间的整合和拮抗相互作用都有助于端脑的模式形成。
