Expression of Disabled 1 suppresses astroglial differentiation in neural stem cells

Mol Cell Neurosci. 2009 Jan;40(1):50-61. doi: 10.1016/j.mcn.2008.08.012. Epub 2008 Sep 18.

Abstract

Disabled 1 (Dab1), a cytoplasmic adaptor protein expressed predominantly in the CNS, transduces a Reelin-initiated signaling that controls neuronal migration and positioning during brain development. To determine the role of Dab1 in neural stem cell (NSC) differentiation, we established a culture of neurospheres derived from the embryonic forebrain of the Dab1(-/-) mice, yotari. Differentiating Dab1(-/-) neurospheres exhibited a higher expression of GFAP, an astrocytic marker, at the expense of neuronal markers. Under Dab1-deficient condition, the expression of NeuroD, a transcription factor for neuronal differentiation, was decreased and the JAK-STAT pathway was evidently increased during differentiation of NSC, suggesting the possible involvement of Dab1 in astrocyte differentiation via JAK-STAT pathway. Notably, expression of neural and glial markers and the level of JAK-STAT signaling molecules were not changed in differentiating NSC by Reelin treatment, indicating that differentiation of NSC is Reelin-independent. Immunohistochemical analyses showed a decrease in the number of neurons and an increase in the number of GFAP-positive cells in developing yotari brains. Our results suggest that Dab1 participates in the differentiation of NSCs into a specific cell lineage, thereby maintaining a balance between neurogenesis and gliogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / physiology*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Cell Culture Techniques
  • Cell Differentiation / physiology*
  • Cell Lineage
  • Cells, Cultured
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • Intermediate Filament Proteins / genetics
  • Intermediate Filament Proteins / metabolism
  • Janus Kinases / genetics
  • Janus Kinases / metabolism*
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nestin
  • Neurons / cytology
  • Neurons / physiology*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Reelin Protein
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / metabolism*
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism
  • Stem Cells / cytology
  • Stem Cells / physiology*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Adhesion Molecules, Neuronal
  • Dab1 protein, mouse
  • Extracellular Matrix Proteins
  • Intermediate Filament Proteins
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nestin
  • RNA, Small Interfering
  • Reelin Protein
  • STAT Transcription Factors
  • Neurogenic differentiation factor 1
  • Janus Kinases
  • Reln protein, mouse
  • Serine Endopeptidases