Lhx2 selector activity specifies cortical identity and suppresses hippocampal organizer fate.

Lhx2 selector activity specifies cortical identity and suppresses hippocampal organizer fate.
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DOI:
10.1126/science.1151695
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发表时间:
2008-01-18
期刊:
影响因子:
56.9
通讯作者:
Monuki, Edwin S.
Monuki, Edwin S.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Mangale, Vishakha S.;Hirokawa, Karla E.;Satyaki, Prasad R. V.;Gokulchandran, Nandini;Chikbire, Satyadeep;Subramanian, Lakshmi;Shetty, Ashwin S.;Martynoga, Ben;Paul, Jolly;Mai, Mark V.;Li, Yuqing;Flanagan, Lisa A.;Tole, Shubha;Monuki, Edwin S.

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创造大脑皮层的最早步骤是将神经上皮指定为皮质的命运。利用小鼠的遗传嵌合体和定时失活,我们证明了LHX2是一个经典的选择器基因,也是皮层特性的基本内在决定因素。LHX2选择器的活性被限制在干细胞组成皮质神经上皮的早期关键时期,在那里它以空间依赖的方式自主地作用于细胞以确定皮质的身份和抑制可供选择的命运。从侧面看,LHX2缺失细胞具有抗HAME的特性,而在内侧则成为皮质HEM细胞,可以诱导和组织异位海马区。除了为LHX2选择器的活性提供功能证据外,这些发现还表明皮质HEM是海马区的组织者。
The earliest step in creating the cerebral cortex is the specification of neuroepithelium to a cortical fate. Using mouse genetic mosaics and timed inactivations, we demonstrate that Lhx2 acts as a classic selector gene and essential intrinsic determinant of cortical identity. Lhx2 selector activity is restricted to an early critical period when stem cells comprise the cortical neuroepithelium, where it acts cell-autonomously to specify cortical identity and suppress alternative fates in a spatially dependent manner. Laterally, Lhx2 null cells adopt antihem identity, whereas medially they become cortical hem cells, which can induce and organize ectopic hippocampal fields. In addition to providing functional evidence for Lhx2 selector activity, these findings show that the cortical hem is a hippocampal organizer.
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