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
Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India.
Science. 2008 Jan 18;319(5861):304-9. doi: 10.1126/science.1151695.
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 demonstrated 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.
大脑皮层形成的最早步骤是神经上皮细胞被指定为皮层命运。利用小鼠基因嵌合体和定时失活技术，我们证明Lhx2作为一个经典的选择基因，是皮层身份的重要内在决定因素。Lhx2的选择活性仅限于干细胞构成皮层神经上皮的早期关键时期，在这个时期它以细胞自主的方式发挥作用，以指定皮层身份并以空间依赖的方式抑制其他命运。在外侧，Lhx2缺失的细胞采用抗脑身份，而在内侧它们变成皮层下托细胞，后者可诱导并组织异位海马区。除了为Lhx2的选择活性提供功能证据外，这些发现还表明皮层下托是海马的组织者。
