Wnt signaling and its downstream target N-myc regulate basal progenitors in the developing neocortex.

Publication Type:

Journal Article

Source:

Development (Cambridge, England), Volume 137, Issue 7, p.1035-44 (2010)

Keywords:

2010, Animals, Basic Sciences Division, beta Catenin, Cell Differentiation, Cell Lineage, Cell Proliferation, Cells, Cultured, Center-Authored Paper, Gene Deletion, MICE, Mice, Transgenic, Multipotent Stem Cells, Neocortex, NEURONS, Proto-Oncogene Proteins c-myc, Signal Transduction, Wnt Proteins

Abstract:

Basal progenitors (also called non-surface dividing or intermediate progenitors) have been proposed to regulate the number of neurons during neocortical development through expanding cells committed to a neuronal fate, although the signals that govern this population have remained largely unknown. Here, we show that N-myc mediates the functions of Wnt signaling in promoting neuronal fate commitment and proliferation of neural precursor cells in vitro. Wnt signaling and N-myc also contribute to the production of basal progenitors in vivo. Expression of a stabilized form of beta-catenin, a component of the Wnt signaling pathway, or of N-myc increased the numbers of neocortical basal progenitors, whereas conditional deletion of the N-myc gene reduced these and, as a likely consequence, the number of neocortical neurons. These results reveal that Wnt signaling via N-myc is crucial for the control of neuron number in the developing neocortex.