Sip1 Downstream Effector ninein Controls Neocortical Axonal Growth, Ipsilateral Branching, and Microtubule Growth and Stability
Sip1 Downstream Effector ninein Controls Neocortical Axonal Growth, Ipsilateral Branching, and Microtubule Growth and Stability
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DOI：
10.1016/j.neuron.2015.01.018
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发表时间：
2015-03
期刊：
影响因子：
16.2
通讯作者：
S. Srivatsa;Srinivas Parthasarathy;Z. Molnár;V. Tarabykin
中科院分区：
文献类型：
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作者：
S. Srivatsa;Srinivas Parthasarathy;Z. Molnár;V. Tarabykin
Sip 1是一种重要的转录因子，调节CNS发育的几个方面。人类SIP 1基因突变与Mowat-Wilson综合征（MWS）有关，MWS的特征是严重的智力迟钝和胼胝体发育不全。在这项研究中，我们发现Sip 1对小鼠前脑皮质内、皮质间和皮质-皮质下联系的形成至关重要，新皮质中所有有丝分裂后神经元的Sip 1缺失导致胼胝体、前连合和皮质脊髓束形成的缺失。新皮质中Sip 1的嵌合缺失揭示了轴突生长和同侧皮质内侧支形成的缺陷。sip 1通过其直接下游效应子ninein（一种微管结合蛋白）介导这些效应。Ninein又通过影响微管的稳定性和动力学来影响轴突生长和分支的速率。
Sip1 is an important transcription factor that regulates several aspects of CNS development. Mutations in the humanSIP1gene have been implicated in Mowat-Wilson syndrome (MWS), characterized by severe mental retardation and agenesis of the corpus callosum. In this study we have shown thatSip1is essential for the formation of intracortical, intercortical, and cortico-subcortical connections in the murine forebrain.Sip1deletion from all postmitotic neurons in the neocortex results in lack of corpus callosum, anterior commissure, and corticospinal tract formation. Mosaic deletion ofSip1in the neocortex reveals defects in axonal growth and in ipsilateral intracortical-collateral formation. Sip1 mediates these effects through its direct downstream effector ninein, a microtubule binding protein. Ninein in turn influences the rate of axonal growth and branching by affecting microtubule stability and dynamics.