Yun Kyuson, Garel Sonia, Fischman Seth, Rubenstein John L R
Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, LPPI, University of California at San Francisco, San Francisco, California 94143-0984, USA.
J Comp Neurol. 2003 Jun 23;461(2):151-65. doi: 10.1002/cne.10685.
The function of the Gsh1 and Gsh2 homeobox transcription factors during development of the mouse telencephalon was studied using loss of function mutations. No telencephalic phenotype was observed in Gsh1 mutants, whereas Gsh2 and Gsh1/2 mutants showed progressively more severe defects in development of neurons derived from the lateral ganglionic eminence (LGE). These defects arise from abnormal dorsoventral specification of LGE progenitor cells. Mice lacking both Gsh1 and Gsh2 have severe hypoplasia of the striatum, olfactory tubercle, and interneurons that migrate from the dorsal LGE to the olfactory bulb. In addition, Gsh function is linked to the development of telencephalic dopaminergic neurons. These observations show that Gsh1 and Gsh2 have early roles in defining the identity of LGE progenitor cells. As a result of the basal ganglia defects in the Gsh1/2 mutants, there are pallial heterotopia near the cortical/subcortical limit and defects in the pathfinding of corticofugal and thalamocortical fibers. These findings highlight the developmental interdependence of adjacent telencephalic structures.
利用功能丧失突变研究了Gsh1和Gsh2同源盒转录因子在小鼠端脑发育过程中的作用。在Gsh1突变体中未观察到端脑表型，而Gsh2和Gsh1/2突变体在源自外侧神经节隆起（LGE）的神经元发育中表现出逐渐加重的缺陷。这些缺陷源于LGE祖细胞背腹向特化异常。同时缺失Gsh1和Gsh2的小鼠纹状体、嗅结节以及从背侧LGE迁移至嗅球的中间神经元严重发育不全。此外，Gsh功能与端脑多巴胺能神经元的发育有关。这些观察结果表明，Gsh1和Gsh2在确定LGE祖细胞的特性方面具有早期作用。由于Gsh1/2突变体中基底神经节存在缺陷，在皮质/皮质下边界附近出现皮质异位，并且皮质传出纤维和丘脑皮质纤维的路径寻找存在缺陷。这些发现突出了相邻端脑结构在发育上的相互依赖性。
