大脑皮层是大脑最大最复杂的组成部分，哺乳动物——尤其是人类，具有高度发达的大脑皮层。虽然已知组成大脑皮层的神经元最初都是由干细胞分化而来，并且不可逆地形成大脑皮层各个不同区域，但干细胞分化成各类神经元的机制一直是科学界还未解开的谜团。

索尔克生物研究所的科学家在一篇发表于10月11日Nature Neuroscience杂志上，首次发现关于上述问题的遗传机制。他们发现，LIM同源结构域转录因子Lhx2(LIM homeodomain transcription factor Lhx2  )在某一关键期能够决定干细胞分化的命运。

胚胎时期的大脑发育经历着不同的阶段：从万能干细胞(omnipotent stem cells)到大脑皮层祖细胞(cortical progenitor cells)，最终分化为不同的功能区。在神经形成(neurogenesis)早期，神经上皮细胞(neuroepithelial cells)通过对称分裂，形成神经上皮细胞库，然后分化为放射状胶质细胞(radial glia)，该细胞分化形成的神经元组成大脑各个功能区的灰质(gray matter)。

之前有研究发现生长因子Fgf10控制着神经上皮细胞向放射状胶质细胞的分化时间。而在接下去的分化方向上，研究人员猜测，同源结构域转录因子Lhx2起着重要的作用。为了验证该假设，研究人员在老鼠胚胎干细胞不同发育阶段剔除Lhx2。

研究发现，当神经上皮细胞分化为放射状胶质细胞过程中剔除Lhx2，新大脑皮层转化为嗅觉皮层。而比上述试验晚一天进行的试验中，并未出现上述转化结果。该研究结果表明，Lhx2控制着干细胞向嗅觉皮层的方向分化。（生物谷Bioon.com）

生物谷推荐原始出处：

Nature Neuroscience 11 October 2009 | doi:10.1038/nn.2427

Lhx2 specifies regional fate in Emx1 lineage of telencephalic progenitors generating cerebral cortex

Shen-Ju Chou1, Carlos G Perez-Garcia1, Todd T Kroll1 & Dennis D M O'Leary1

Cerebral cortex is comprised of regions, including six-layer neocortex and three-layer olfactory cortex, generated by telencephalic progenitors of an Emx1 lineage. The mechanism specifying region-specific subpopulations in this lineage is unknown. We found that the LIM homeodomain transcription factor Lhx2 in mice, expressed in graded levels by progenitors, determines their regional identity and fate decisions to generate neocortex or olfactory cortex. Deletion of Lhx2 with Emx1-cre at embryonic day 10.5 (E10.5) altered the fates of progenitors, causing them to generate three-layer cortex, phenocopying olfactory cortex rather than lateral neocortex. Progenitors did not generate ectopic olfactory cortex following Lhx2 deletion at E11.5. Thus, Lhx2 regulates a regional-fate decision by telencephalic progenitors during a critical period that ends as they differentiate from neuroepithelial cells to neuronogenic radial glia. These findings establish a genetic mechanism for determining regional-fate in the Emx1 lineage of telencephalic progenitors that generate cerebral cortex.

1 Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, California, USA.

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