Dlx transcription factors promote migration through repression of axon and dendrite growth
Dlx transcription factors promote migration through repression of axon and dendrite growth
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DOI：
10.1016/j.neuron.2007.05.024
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发表时间：
2007-06-21
期刊：
影响因子：
16.2
通讯作者：
Rubenstein, John L. R.
中科院分区：
文献类型：
--
作者：
Cobos, Inma;Borello, Ugo;Rubenstein, John L. R.
在小鼠端脑中，DIx同源框转录因子对于苍白球下衍生的GABA能中间神经元向新皮质的切向迁移是必不可少的。然而，这一过程的机制知之甚少。在这里，我们证明了DIx 1/2在抑制苍白球下衍生的未成熟中间神经元的轴突生长中具有核心作用，当它们切向迁移到皮层时。在DIx 1（-/-）;DIx（2-/-）突变体中，神经突长度增加，细胞无法迁移。在DIx 1（-/-）中; DIx 2（+/-）突变体，而未成熟的中间神经元的切线迁移似乎正常，他们开发的树突和轴突过程的长度增加和减少分支，并在其新皮质层的位置有缺陷。因此，需要DIx 1/2来协调神经突成熟和迁移的程序。在这方面，我们提供的遗传证据表明，在未成熟的中间神经元DIx 1/2抑制p21激活的丝氨酸/苏氨酸激酶PAK 3，下游效应的Rho家族的GTP酶，是至关重要的抑制轴突生长和促进切线迁移。
In the mouse telencephalon, DIx homeobox transcription factors are essential for the tangential migration of subpallial-derived GABAergic interneurons to neocortex. However, the mechanisms underlying this process are poorly understood. Here, we demonstrate that DIx1/2 has a central role in restraining neurite growth of subpallial-derived immature interneurons at a stage when they migrate tangentially to cortex. In DIx1(-/-);DIx(2-/-) mutants, neurite length is increased and cells fail to migrate. In DIx1(-/-); DIx2(+/-) mutants, while the tangential migration of immature interneurons appears normal, they develop dendritic and axonal processes with increased length and decreased branching, and have deficits in their neocortical laminar positions. Thus, DIx1/2 is required for coordinating programs of neurite maturation and migration. In this regard, we provide genetic evidence that in immature interneurons DIx1/2 repression of the p21-activated serine/threonine kinase PAK3, a downstream effector of the Rho family of GTPases, is critical in restraining neurite growth and promoting tangential migration.