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

Development. 2010 Apr;137(7):1035-44. doi: 10.1242/dev.046417.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Cell Lineage
  • Cell Proliferation
  • Cells, Cultured
  • Gene Deletion
  • Mice
  • Mice, Transgenic
  • Multipotent Stem Cells / cytology
  • Multipotent Stem Cells / physiology*
  • Neocortex / cytology*
  • Neocortex / embryology*
  • Neocortex / metabolism
  • Neurons / cytology
  • Neurons / physiology
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Signal Transduction / physiology*
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • Proto-Oncogene Proteins c-myc
  • Wnt Proteins
  • beta Catenin