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Cerebral Cortex Advance Access originally published online on April 14, 2009
Cerebral Cortex 2009 19(Supplement 1):i62-i69; doi:10.1093/cercor/bhp030
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© The Author 2009. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

This article appears in the following Cerebral Cortex issue: Cortical Development: Neural Stem Cells to Neural Circuits Chania, Greece, May 22-25, 2008 [View the issue table of contents]

Lmo4 and Clim1 Progressively Delineate Cortical Projection Neuron Subtypes during Development

Eiman Azim1,2,3, Sara J. Shnider1,2,3,4, Gustav Y. Cederquist1,2,3, U. Shivraj Sohur1,2,3 and Jeffrey D. Macklis1,2,3

1 MGH-HMS Center for Nervous System Repair, Departments of Neurosurgery and Neurology, Program in Neuroscience, Harvard Medical School, Boston, MA 02114, USA, 2 Nayef Al-Rodhan Laboratories, Massachusetts General Hospital, Boston, MA 02114, USA, 3 Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA, 4 Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA

Address correspondence to email: jeffrey_macklis{at}hms.harvard.edu.

Molecular controls over the development of the exceptional neuronal subtype diversity of the cerebral cortex are now beginning to be identified. The initial subtype fate decision early in the life of a neuron, and the malleability of this fate when the balance of key postmitotic signals is modified, reveals not only that a neuron is deterministically set on a general developmental path at its birth, but also that this program must be precisely executed during postmitotic differentiation. Here, we show that callosal projection neurons (CPN) and subcerebral projection neurons (subcerebral PN) in layer V of the neocortex share aspects of molecular identity after their birth that are progressively resolved during differentiation. The LIM-homeodomain–related genes Lmo4 and Clim1 are initially expressed by both CPN and subcerebral PN in layer V, and only during mid to late differentiation does expression of Lmo4 and Clim1 become largely segregated into distinct neuronal subtypes. This progressive postmitotic resolution of molecular identity reveals similarities and possibly shared evolutionary origin between layer V CPN and subcerebral PN, and provides insight into how and when these neuronal subtypes achieve their distinct identities during cortical development.

Key Words: callosal • corticospinal • cortical development • Lmo4Clim1Ldb2 • subcerebral • subtype identity


Eiman Azim and Sara J. Shnider contributed equally to this work.


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