Navigating Neocortical Neurogenesis and Neuronal Specification: A Positional Information System Encoded by Neurogenetic Gradients

Abstract

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.