Zic1 levels regulate mossy fiber neuron position and axon laterality choice in the ventral brain stem.
Zic1 levels regulate mossy fiber neuron position and axon laterality choice in the ventral brain stem.
复制标题
ZIC1水平调节腹侧脑干中的苔藓纤维神经元位置和轴突侧性选择。
DOI：
10.1016/j.neuroscience.2009.02.082
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发表时间：
2009-09-01
期刊：
影响因子：
3.3
通讯作者：
中科院分区：
文献类型：
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作者：
脑干的脑桥灰质神经元是苔藓纤维（MF）传入小脑颗粒细胞的主要来源。实现这种连通性涉及脑桥灰质神经元细胞体在脑干脑桥核内的早期区域化，以及建立对侧与同侧小脑领土的交叉与非交叉MF投影的适当比例。在这里，我们报告的转录因子Zic 1在新的有丝分裂后脑桥灰质神经元的表达，并在胚胎和出生后的小鼠，牵连Zic 1水平作为一个关键的决定因素脑桥和轴突偏侧脑桥神经元细胞体的位置目前的功能实验。减少Zic 1水平胚胎通过在子宫内电穿孔的短发夹RNA干扰（shRNA）载体转移出生后的脑桥神经元的分布从尾外侧的rostromedial领土;相比之下，增加Zic 1水平导致的相互转变，与电穿孔的细胞重新分布尾外侧。与后者相关的是轴突偏侧性的变化，更大比例的显着预测现在针对同侧而不是对侧小脑。因此，脑桥灰质神经元中的Zic 1水平在脑桥小脑回路的发育中起重要作用。
Pontine gray neurons of the brain stem are a major source of mossy fiber (MF) afferents to granule cells of the cerebellum. Achieving this connectivity involves an early regionalization of pontine gray neuron cell bodies within the brainstem pontine nuclei, as well as establishing the proper ratio of crossed versus uncrossed MF projections to contralateral versus ipsilateral cerebellar territories. Here, we report expression of the transcription factor Zic1 in newly postmitotic pontine gray neurons and present functional experiments in embryonic and postnatal mice that implicate Zic1 levels as a key determinant of pontine neuron cell body position within the pons and axon laterality. Reducing Zic1 levels embryonically via in utero electroporation of short hairpin RNA interference (shRNAi) vectors shifted the postnatal distribution of pontine neurons from caudolateral to rostromedial territories; by contrast, increasing Zic1 levels resulted in the reciprocal shift, with electroporated cells redistributing caudolaterally. Associated with the latter was a change in axon laterality, with a greater proportion of marked projections now targeting the ipsilateral instead of contralateral cerebellum. Zic1 levels in pontine gray neurons, therefore, play an important role in the development of pontocerebellar circuitry.