TGF-beta1/SMAD signaling induces astrocyte fate commitment in vitro: implications for radial glia development

Glia. 2007 Aug 1;55(10):1023-33. doi: 10.1002/glia.20522.

Abstract

Radial glial (RG) cells are specialized type of cell, which functions as neuronal precursors and scaffolding guides to migrating neurons during cerebral cortex development. After neurogenesis and migration are completed, most of RG cells transform into astrocytes. Mechanism and molecules involved in this process are not completely elucidated. We previously demonstrated that neurons activate the promoter of the astrocyte maturation marker GFAP in astrocytes by secretion of transforming growth factor beta 1 (TGF-beta1) in vitro. Here, we studied the role of neurons and TGF-beta1 pathway in RG differentiation. To address this question, we employed cortical progenitor cultures enriched in GLAST/nestin double-labeled cells, markers of RG cells. TGF-beta1 and conditioned medium derived from neuron-astrocyte cocultures (CM) decreased the number of cells expressing the precursor marker nestin and increased that expressing GFAP in cortical progenitor cultures. These events were impaired by addition of neutralizing antibodies against TGF-beta1. Increase in the number of GFAP positive cells was associated with Smads 2/3 nuclear translocation, a hallmark of TGF-beta1 pathway activation. PCR-assays revealed a decrease in the levels of mRNA for the RG marker, BLBP (brain lipid binding protein), due to TGF-beta1 and CM treatment. We further identified TGF-beta1 receptor in cortical progenitor cultures suggesting that these cells might be target for TGF-beta1 during development. Our work provides strong evidence that TGF-beta1 might be a novel factor involved in RG-astrocyte transformation and highlights the role of neuron-glia interaction in this process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Active Transport, Cell Nucleus / physiology
  • Animals
  • Animals, Newborn
  • Astrocytes / cytology
  • Astrocytes / metabolism*
  • Biomarkers / metabolism
  • Cell Communication / drug effects
  • Cell Communication / physiology
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Lineage / drug effects
  • Cell Lineage / physiology
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / embryology
  • Cerebral Cortex / metabolism*
  • Coculture Techniques
  • Culture Media, Conditioned / pharmacology
  • Fatty Acid-Binding Protein 7
  • Fatty Acid-Binding Proteins / genetics
  • Glial Fibrillary Acidic Protein / metabolism
  • Mice
  • Nerve Tissue Proteins / genetics
  • Neuroglia / cytology
  • Neuroglia / metabolism*
  • Neurons / metabolism
  • Receptors, Transforming Growth Factor beta / drug effects
  • Receptors, Transforming Growth Factor beta / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Smad Proteins / metabolism*
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism*
  • Transforming Growth Factor beta1 / metabolism*
  • Transforming Growth Factor beta1 / pharmacology

Substances

  • Biomarkers
  • Culture Media, Conditioned
  • Fabp7 protein, mouse
  • Fatty Acid-Binding Protein 7
  • Fatty Acid-Binding Proteins
  • Glial Fibrillary Acidic Protein
  • Nerve Tissue Proteins
  • Receptors, Transforming Growth Factor beta
  • Smad Proteins
  • Transforming Growth Factor beta1