The Gsh2 homeodomain gene controls multiple aspects of telencephalic development.
The Gsh2 homeodomain gene controls multiple aspects of telencephalic development.
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发表时间：
2000-12
期刊：
影响因子：
4.6
通讯作者：
J. Corbin;N. Gaiano;R. Machold;A. Langston;G. Fishell
中科院分区：
文献类型：
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作者：
J. Corbin;N. Gaiano;R. Machold;A. Langston;G. Fishell
最近已证明同源框基因对于哺乳动物端脑的正确模式很重要。这些基因之一是 Gsh2，其在前脑中的表达仅限于腹侧区域。在这项研究中，我们证明 Gsh2 是 sonic eager 的下游靶标，缺乏 Gsh2 会导致端脑发育的严重缺陷。 Gsh2 突变体的许多基因的表达显着降低，这些基因标志着外侧神经节隆起（纹状体原基）的早期发育。伴随着模式基因的早期丢失，背侧端脑标记最初穿过皮质-纹状体边界扩展到外侧神经节隆起。有趣的是，随着发育的进行，这种早期标记物的丢失会得到补偿，这与皮质-纹状体边界的分子重建同时发生。尽管有这种补偿，纹状体神经元不同亚群的发育仍存在缺陷。此外，虽然我们的分析表明，Gsh2突变体中腹侧衍生的中间神经元向发育中的大脑皮层的迁移没有受到显着影响，但嗅球中GABA能中间神经元的出现明显延迟。总而言之，我们的数据支持一个模型，其中 Gsh2 响应声音刺猬信号，在端脑发育的多个方面发挥着至关重要的作用。
Homeobox genes have recently been demonstrated to be important for the proper patterning of the mammalian telencephalon. One of these genes is Gsh2, whose expression in the forebrain is restricted to the ventral domain. In this study, we demonstrate that Gsh2 is a downstream target of sonic hedgehog and that lack of Gsh2 results in profound defects in telencephalic development. Gsh2 mutants have a significant decrease in the expression of numerous genes that mark early development of the lateral ganglionic eminence, the striatal anlage. Accompanying this early loss of patterning genes is an initial expansion of dorsal telencephalic markers across the cortical-striatal boundary into the lateral ganglionic eminence. Interestingly, as development proceeds, there is compensation for this early loss of markers that is coincident with a molecular re-establishment of the cortical-striatal boundary. Despite this compensation, there is a defect in the development of distinct subpopulations of striatal neurons. Moreover, while our analysis suggests that the migration of the ventrally derived interneurons to the developing cerebral cortex is not significantly affected in Gsh2 mutants, there is a distinct delay in the appearance of GABAergic interneurons in the olfactory bulb. Taken together, our data support a model in which Gsh2, in response to sonic hedgehog signaling, plays a crucial role in multiple aspects of telencephalic development.