The mouse homeobox gene Gbx2 is required for the development of cholinergic interneurons in the striatum.
The mouse homeobox gene Gbx2 is required for the development of cholinergic interneurons in the striatum.
复制标题
DOI：
10.1523/jneurosci.3742-10.2010
复制
发表时间：
2010-11-03
期刊：
影响因子：
--
通讯作者：
Li JY
中科院分区：
文献类型：
--
作者：
Chen L;Chatterjee M;Li JY
哺乳动物前脑胆碱能神经元由纹状体的局部环路神经元和基底前脑的投射神经元组成。已知这些神经元来自主要位于内侧神经节隆起（MGE）中的共同祖细胞库。然而，很少有人知道的遗传程序，区分这两种类型的胆碱能神经元。使用诱导的遗传命运映射，在这里，我们研究了在MGE中表达同源结构域转录因子Gbx2的细胞的发育命运。我们发现，Gbx2谱系衍生的细胞，进行切线迁移专门引起几乎所有的胆碱能中间神经元在纹状体，而那些进行径向迁移主要产生非胆碱能神经元在基底前脑。Gbx2在整个小鼠胚胎或特别是在MGE中的缺失导致纹状体中胆碱能神经元的异常分布和显著减少。我们发现，早期出生的胆碱能中间神经元优先填充纹状体的侧面和成熟早于晚出生的神经元，通常居住在纹状体的内侧部分。在没有Gbx2的情况下，早期出生的纹状体胆碱能前体显示异常的神经突生长和增加的复杂性，并异常有助于内侧的尾壳核，而晚出生的（胚胎12.5天后）纹状体胆碱能中间神经元在很大程度上失踪。总之，我们的数据表明，Gbx2是必需的纹状体胆碱能中间神经元的发展，也许通过调节纹状体胆碱能前体的切线迁移。
Mammalian forebrain cholinergic neurons are composed of local circuit neurons in the striatum and projection neurons in the basal forebrain. These neurons are known to arise from a common pool of progenitors that primarily resides in the medial ganglionic eminence (MGE). However, little is known about the genetic programs that differentiate these two types of cholinergic neurons. Using inducible genetic fate mapping, here we have examined the developmental fate of cells that express the homeodomain transcription factor Gbx2 in the MGE. We show that the Gbx2 lineage-derived cells that undergo tangential migration exclusively give rise to almost all cholinergic interneurons in the striatum, while those undergoing radial migration mainly produce non-cholinergic neurons in the basal forebrain. Deletion of Gbx2 throughout the mouse embryo or specifically in the MGE results in abnormal distribution and significant reduction of cholinergic neurons in the striatum. We show that early-born cholinergic interneurons preferentially populate the lateral aspect of the striatum and mature earlier than late-born neurons, which normally reside in the medial part of the striatum. In the absence of Gbx2, early-born striatal cholinergic precursors display abnormal neurite outgrowth and increased complexity, and abnormally contribute to the medial of the caudate-putamen, while late-born (after embryonic day 12.5) striatal cholinergic interneurons are largely missing. Together, our data demonstrate that Gbx2 is required for development of striatal cholinergic interneurons, perhaps by regulating tangential migration of the striatal cholinergic precursors.