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The Journal of Neuroscience, October 3, 2007, 27(40):10777-10784; doi:10.1523/JNEUROSCI.3091-07.2007

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Development/Plasticity/Repair
Navigating Neocortical Neurogenesis and Neuronal Specification: A Positional Information System Encoded by Neurogenetic Gradients

Bernhard Suter,¹ Richard S. Nowakowski,² Pradeep G. Bhide,¹ and Verne S. Caviness¹

¹Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts 02114, and ²Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey–Robert Wood Johnson Medical School, Piscataway, New Jersey 08854

Correspondence should be addressed to Dr. Verne S. Caviness, Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, VBK-901, Boston, MA 02114. Email: caviness{at}helix.mgh.harvard.edu

The projection neurons of the neocortex are produced in the pseudostratified ventricular epithelium (PVE) lining the embryonic lateral ventricles. Over a 7 d period in mouse, these neurons arise in an overlapping layer VI-to-II sequence and in an anterolateral to posteromedial gradient [the transverse neurogenetic gradient (TNG)]. At any time in the 7 d neurogenetic interval, a given PVE cell must know what class of precursor cell or neuron to form next. How this information is encoded in the PVE is not known. With comparative experiments in wild-type and double-transgenic mice, overexpressing the cell cycle inhibitor p27^Kip1, we show that a gradient of expression of Lhx2 (inferred from its mRNA levels), a LIM homeodomain transcription factor, together with a gradient in duration of the G₁ phase of the cell cycle (T_G1), are sufficient to specify a positional mapping system that informs the PVE cell what class of neuron to produce next. Lhx2 likely is representative of an entire class of transcription factors expressed along the TNG. This mapping system consisting of a combination of signals from two different sources is a novel perspective on the source of positional information for neuronal specification in the developing CNS.

Key words: positional information; neocortex; neurogenesis; cell cycle; Lhx2 expression; transverse neurogenetic gradient

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Received March 13, 2007; revised Aug. 14, 2007; accepted Aug. 15, 2007.

Correspondence should be addressed to Dr. Verne S. Caviness, Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, VBK-901, Boston, MA 02114. Email: caviness{at}helix.mgh.harvard.edu

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