Sonic hedgehog is a chemoattractant for midbrain dopaminergic axons.
Sonic hedgehog is a chemoattractant for midbrain dopaminergic axons.
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DOI：
10.1371/journal.pone.0007007
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发表时间：
2009-09-23
期刊：
影响因子：
3.7
通讯作者：
Abeliovich A
中科院分区：
文献类型：
--
作者：
Hammond R;Blaess S;Abeliovich A
中脑多巴胺能轴突从黑质（SN）和腹侧被盖区（VTA）投射到吻侧靶组织，包括纹状体、苍白球和下丘脑。位于内侧的腹侧被盖区的轴突主要投射到前脑中更内侧的目标组织，而更外侧的SN轴突则投射到包括背外侧纹状体在内的外侧目标。这种结构多样性是这些途径不同功能的基础。虽然一些指导线索已经牵连在形成的SN和VTA的不同轴突投射，其多样性的分子基础仍然不清楚。在这里，我们调查的mDN轴突投射的结构多样性的分子基础。我们发现，刺猬（Shh）的表达在一个选择点的过程中的吻多巴胺能投射。此外，在中脑外植体中，多巴胺能投射被吸引到Shh源。最后，在Shh信号在神经元发育后期失活的小鼠中，最内侧的多巴胺能投射是缺乏的。除了Shh在诱导mDN前体中的作用之外，Shh在多巴胺能轴突到吻侧靶组织的寻路中起重要作用。此外，Shh信号参与确定这些多巴胺能投射的结构多样性。
Midbrain dopaminergic axons project from the substantia nigra (SN) and the ventral tegmental area (VTA) to rostral target tissues, including the striatum, pallidum, and hypothalamus. The axons from the medially located VTA project primarily to more medial target tissues in the forebrain, whereas the more lateral SN axons project to lateral targets including the dorsolateral striatum. This structural diversity underlies the distinct functions of these pathways. Although a number of guidance cues have been implicated in the formation of the distinct axonal projections of the SN and VTA, the molecular basis of their diversity remains unclear. Here we investigate the molecular basis of structural diversity in mDN axonal projections. We find that Sonic Hedgehog (Shh) is expressed at a choice point in the course of the rostral dopaminergic projections. Furthermore, in midbrain explants, dopaminergic projections are attracted to a Shh source. Finally, in mice in which Shh signaling is inactivated during late neuronal development, the most medial dopaminergic projections are deficient. In addition to the role of Shh in the induction of mDN precursors, Shh plays an important role in dopaminergic axon pathfinding to rostral target tissues. Furthermore, Shh signaling is involved in determining the structural diversity of these dopaminergic projections.
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影响因子：
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ROSENTHAL, A
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