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Science 18 January 2008:
Vol. 319. no. 5861, pp. 304 - 309
DOI: 10.1126/science.1151695
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Research Articles

Lhx2 Selector Activity Specifies Cortical Identity and Suppresses Hippocampal Organizer Fate

Vishakha S. Mangale,1* Karla E. Hirokawa,2* Prasad R. V. Satyaki,1* Nandini Gokulchandran,1* Satyadeep Chikbire,1 Lakshmi Subramanian,1 Ashwin S. Shetty,1 Ben Martynoga,1 Jolly Paul,1 Mark V. Mai,3 Yuqing Li,4 Lisa A. Flanagan,5 Shubha Tole,1{dagger} Edwin S. Monuki2,5{dagger}

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.

1 Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India.
2 Department of Developmental and Cell Biology, School of Biological Sciences, University of California Irvine, Irvine, CA 92697, USA.
3 Department of Biology, Swarthmore College, Swarthmore, PA 19081, USA.
4 Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
5 Department of Pathology and Laboratory Medicine, School of Medicine, University of California Irvine, Irvine, CA 92697, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: emonuki{at}uci.edu (E.S.M., cKO component); stole{at}tifr.res.in (S.T., ESC chimeras)

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