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Cerebral Cortex Advance Access originally published online on March 30, 2005
Cerebral Cortex 2005 15(12):2021-2028; doi:10.1093/cercor/bhi077
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© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oupjournals.org

A Mutually Stimulating Loop Involving Emx2 and Canonical Wnt Signalling Specifically Promotes Expansion of Occipital Cortex and Hippocampus

L. Muzio1, J.M. Soria1, M. Pannese1, S. Piccolo2 and A. Mallamaci1

1 Istituto Scientifico H San Raffaele, DIBIT, via Olgettina 58, 20132 Milan, Italy and 2 Department of Medical Biotechnology, University of Padua, viale Colombo 3, 35100 Padua, Italy

The present address for J. M. Soria is Hospital general universitario Avenida Tres Cruces s/n, 46014 Valencia, Spain. Address correspondence to Antonello Mallamaci, Istituto Scientifico H San Raffaele, DIBIT, via Olgettina 58, 20132 Milan, Italy. Email: a.mallamaci{at}hsr.it.

The correct size of the different areas composing the mature cerebral cortex depends on the proper early allocation of cortical progenitors to their distinctive areal fates, as well as on appropriate subsequent tuning of their area-specific proliferation–differentiation profiles. Whereas much is known about the genetics of the former process, the molecular mechanisms regulating proliferation and differentiation rates within distinctive cortical proto-areas are still largely obscure. Here we show that a mutual stimulating loop, involving Emx2 and canonical Wnt signalling, specifically promotes expansion of the occipito-hippocampal anlage. Collapse of this loop occurring in Emx2–/– mutants leads progenitors within this region to slow down DNA synthesis and exit prematurely from the cell cycle, due to misregulation of cell cycle-, proneural- and lateral inhibition-molecular machineries, and eventually results in dramatic and selective size-reduction of occipital cortex and hippocampus. Reactivation of canonical Wnt signalling in the same mutants rescues a subset of molecular abnormalities and corrects differentiation rates of occipito-hippocampal progenitors.

Key Words: areal sizing • Emx2 • Wnt signalling • cell cycle genes • proneural genes


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