Celsr3 and Fzd3 Organize a Pioneer Neuron Scaffold to Steer Growing Thalamocortical Axons.
Celsr3 and Fzd3 Organize a Pioneer Neuron Scaffold to Steer Growing Thalamocortical Axons.
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DOI：
10.1093/cercor/bhw132
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发表时间：
2016-07
期刊：
影响因子：
--
通讯作者：
Zhou L
中科院分区：
文献类型：
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作者：
Feng J;Xian Q;Guan T;Hu J;Wang M;Huang Y;So KF;Evans SM;Chai G;Goffinet AM;Qu Y;Zhou L
Celsr3和Fzd3独立于其在皮质或丘脑神经元中的表达调节丘脑皮质相互投射的发展。为了进一步了解这种细胞非自治机制，我们测试了Celsr3和Fzd3是否可以通过isl1阳性的导柱细胞起作用。在胚胎期(E) 9.5-E10.5， isl1阳性细胞出现在前脑，从E12.5开始，它们在腹侧端脑和丘脑前庭形成2个特遣队。在对照小鼠中，皮质丘脑轴突运行在与isl1阳性细胞密切接触的腹侧端脑走廊。当表达Isl1的细胞中的Celsr3或Fzd3失活时，皮质纤维在Isl1高表达的端脑腹侧走廊中失速并形成环路，丘脑轴突无法穿过间脑-端脑交界处（DTJ）。在E12.5，在丘脑和皮质轴突出现之前，对照而非突变胚胎中，来自isl1阳性细胞的先驱投射从两侧穿过DTJ。这些早期的突起似乎就像一座桥梁，引导后来生长的丘脑轴突通过颞下颌颞叶。我们的数据表明，Celsr3和Fzd3协调了先锋神经元及其轴突支架的形成。这个支架从丘脑前侧延伸到腹侧端脑和皮层下，并引导相互作用的皮质丘脑纤维。
Celsr3 and Fzd3 regulate the development of reciprocal thalamocortical projections independently of their expression in cortical or thalamic neurons. To understand this cell non autonomous mechanism further, we tested whether Celsr3 and Fzd3 could act via Isl1-positive guidepost cells. Isl1-positive cells appear in the forebrain at embryonic day (E) 9.5-E10.5 and, from E12.5, they form 2 contingents in ventral telencephalon and prethalamus. In control mice, corticothalamic axons run in the ventral telencephalic corridor in close contact with Isl1-positive cells. When Celsr3 or Fzd3 is inactivated in Isl1-expressing cells, corticofugal fibers stall and loop in the ventral telencephalic corridor of high Isl1 expression, and thalamic axons fail to cross the diencephalon–telencephalon junction (DTJ). At E12.5, before thalamic and cortical axons emerge, pioneer projections from Isl1-positive cells cross the DTJ from both sides in control but not mutant embryos. These early projections appear to act like a bridge to guide later growing thalamic axons through the DTJ. Our data suggest that Celsr3 and Fzd3 orchestrate the formation of a scaffold of pioneer neurons and their axons. This scaffold extends from prethalamus to ventral telencephalon and subcortex, and steers reciprocal corticothalamic fibers.