Combinatorial function of the homeodomain proteins Nkx2.1 and Gsh2 in ventral telencephalic patterning
Combinatorial function of the homeodomain proteins Nkx2.1 and Gsh2 in ventral telencephalic patterning
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DOI：
10.1242/dev.00717
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发表时间：
2003-10-01
期刊：
影响因子：
4.6
通讯作者：
Fishell, G
中科院分区：
文献类型：
--
作者：
Corbin, JG;Rutlin, M;Fishell, G
哺乳动物端脑的区域模式化需要三个含有同源结构域的转录因子Pax6、Gsh2和Nkx2.1的功能。这些因素是端脑的背侧、外侧和内侧区域发育所必需的。以前的工作表明，两个基因编码这些因素，Pax6和Gsh2，交叉抑制对方之间的边界端脑的背侧和外侧区域的形成。在这里，我们研究是否有类似的相互作用负责建立端脑基因表达的其他边界。令人惊讶的是，尽管在发育的特定时间，Pax6和Gsh2都与Nkx2.1保持互补的表达模式，但在任何情况下，这些边界都不是通过类似的交叉抑制机制来维持的。相反，正如双突变小鼠的分析所揭示的那样，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，如功能丧失和获得分析所示，E10.5后内侧神经节隆起中的Gsh2表达可能负调节Nkx2.1依赖的少突胶质细胞的特异性。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有助于端脑的图案化。
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.