Lhx2 specifies regional fate in Emx1 lineage of telencephalic progenitors generating cerebral cortex.
Lhx2 specifies regional fate in Emx1 lineage of telencephalic progenitors generating cerebral cortex.
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DOI：
10.1038/nn.2427
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发表时间：
2009-11
影响因子：
25
通讯作者：
O'Leary DD
中科院分区：
文献类型：
--
作者：
Chou SJ;Perez-Garcia CG;Kroll TT;O'Leary DD
大脑皮层由Emx1谱系的端脑祖细胞产生的六层新皮层和三层嗅觉皮层组成。在这个谱系中指定特定区域亚群的机制是未知的。我们在小鼠中发现，由祖细胞分级表达的LIM同源结构域转录因子Lhx2决定了它们产生新皮层或嗅皮层的区域身份和命运决定。在E10.5时Lhx2的Emx1-Cre缺失使祖细胞产生三层皮层表型复制嗅皮层而不是外侧新皮层。Lhx2基因在E11.5缺失后，祖细胞不会产生异位嗅皮质。因此，在从神经上皮细胞向神经源性放射状胶质细胞分化的关键时期，Lhx2调节了端脑祖细胞的区域命运决定。祖先对Lhx2的“暴露”可能会决定他们的地区命运。这些发现建立了一种决定产生大脑皮层的端脑祖细胞Emx1谱系区域命运的遗传机制。
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 within this lineage is unknown. We show in mouse that the LIM homeodomain transcription factor Lhx2, expressed in graded levels by progenitors, determines their regional identity and fate decisions to generate neocortex or olfactory cortex. Emx1-Cre deletion of Lhx2 at E10.5 refates progenitors to generate three-layer cortex phenocopying olfactory cortex rather than lateral neocortex. Progenitors do 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 closes as they differentiate from neuroepithelial cells to neuronogenic radial glia. “Exposure” of progenitors to Lhx2 may dictate their regional-fate decisions. These findings establish a genetic mechanism determining regional fate in the Emx1 lineage of telencephalic progenitors that generate cerebral cortex.
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