Reprogramming of postnatal astroglia of the mouse neocortex into functional, synapse-forming neurons

Methods Mol Biol. 2012;814:485-98. doi: 10.1007/978-1-61779-452-0_32.

Abstract

Direct conversion of glia into neurons by cellular reprogramming represents a novel approach toward a cell-based therapy of neurodegenerative processes. Here we describe a protocol that allows for the direct and efficient in vitro reprogramming of mouse astroglia from the early postnatal neocortex by forced expression of single neurogenic fate determinants. By selective retrovirus-mediated expression of neurogenin-2 (Neurog2) on the one hand, or the mouse homologue of Distal-less Dlx2 or the mammalian homologue of achaete-schute-1 (Mash1) on the other, it is possible to drive postnatal astroglia in culture toward the genesis of fully functional, synapse-forming, glutamatergic, i.e., excitatory, and GABAergic, i.e., inhibitory, neurons, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / physiology*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology*
  • Cell- and Tissue-Based Therapy / methods*
  • Homeodomain Proteins / metabolism
  • In Vitro Techniques
  • Mice
  • Neocortex / cytology*
  • Nerve Tissue Proteins / metabolism
  • Neurodegenerative Diseases / therapy*
  • Neurons / cytology*
  • Retroviridae
  • Synapses / physiology*
  • Transcription Factors / metabolism
  • Transduction, Genetic

Substances

  • Ascl1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Distal-less homeobox proteins
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Neurog2 protein, mouse
  • Transcription Factors