Gangemi Rosaria M R, Daga Antonio, Muzio Luca, Marubbi Daniela, Cocozza Serena, Perera Marzia, Verardo Sara, Bordo Domenico, Griffero Fabrizio, Capra Maria C, Mallamaci Antonello, Corte Giorgio
National Institute for Cancer Research, 16132 Genova, Italy.
Eur J Neurosci. 2006 Jan;23(2):325-34. doi: 10.1111/j.1460-9568.2005.04559.x.
Emx2 plays a crucial role in the development of the diencephalon and dorsal telencephalon. Thus, Emx2-null mutants have abnormal cortical lamination and a reduction in size of the caudal and medial areas of the prosencephalon. Emx2 is expressed in neural precursors of the subventricular zone in vivo and in cultured neurospheres in vitro where it controls the size of the transit-amplifying population, affecting proliferation and clonal efficiency of neural stem cells. To identify the cellular processes mastered by Emx2, and possibly the molecular mechanisms by which the gene exerts its action, we compared the expression profile of cultured neurospheres derived from wild-type and Emx2-null mouse embryos. The differential expression of several genes was also confirmed by semiquantitative RT-PCR, real-time PCR and cytofluorimetric analysis in different preparations of neurospheres, and by in situ hybridization. The gene expression profile suggested a role for Emx2 in regulating the differentiation and migration properties of neural precursor cells. This involvement was confirmed in vitro, where the altered clonogenicity and impaired migration of Emx2-null cells were partially corrected by transduction of the Emx2 gene. Taken together, our results indicate that Emx2 is indeed involved in the transition between resident early progenitors (perhaps stem cells) and more mature precursors capable of migrating out of the ventricular zone, becoming postmitotic and differentiating into the appropriate cell type, and help explain the alterations observed in the brains of knock-out mice.
Emx2在间脑和背侧端脑的发育中起关键作用。因此，Emx2基因敲除突变体具有异常的皮质分层，前脑尾侧和内侧区域的大小减小。Emx2在体内脑室下区的神经前体细胞中表达，在体外培养的神经球中也有表达，在那里它控制过渡增殖群体的大小，影响神经干细胞的增殖和克隆效率。为了确定Emx2所掌控的细胞过程，以及该基因发挥作用的可能分子机制，我们比较了来自野生型和Emx2基因敲除小鼠胚胎的培养神经球的表达谱。在不同制备的神经球中，通过半定量RT-PCR、实时PCR和细胞荧光分析，以及原位杂交，也证实了几个基因的差异表达。基因表达谱表明Emx2在调节神经前体细胞的分化和迁移特性中发挥作用。这一作用在体外得到了证实，通过转导Emx2基因，部分纠正了Emx2基因敲除细胞克隆形成能力的改变和迁移受损的情况。综上所述，我们的结果表明，Emx2确实参与了驻留早期祖细胞（可能是干细胞）与能够迁移出脑室区、进入有丝分裂后期并分化为适当细胞类型的更成熟前体细胞之间的转变，并有助于解释在基因敲除小鼠大脑中观察到的变化。
