Mind bomb 1-expressing intermediate progenitors generate notch signaling to maintain radial glial cells

Neuron. 2008 May 22;58(4):519-31. doi: 10.1016/j.neuron.2008.03.018.


Notch signaling is critical for the stemness of radial glial cells (RGCs) during embryonic neurogenesis. Although Notch-signal-receiving events in RGCs have been well characterized, the signal-sending mechanism by the adjacent cells is poorly understood. Here, we report that conditional inactivation of mind bomb-1 (mib1), an essential component for Notch ligand endocytosis, in mice using the nestin and hGFAP promoters resulted in complete loss of Notch activation, which leads to depletion of RGCs, and premature differentiation into intermediate progenitors (IPs) and finally neurons, which were reverted by the introduction of active Notch1. Interestingly, Mib1 expression is restricted in the migrating IPs and newborn neurons, but not in RGCs. Moreover, sorted Mib1+ IPs and neurons can send the Notch signal to neighboring cells. Our results reveal that not only newborn neurons but also IPs are essential Notch-ligand-presenting cells for maintaining RGC stemness during both symmetric and asymmetric divisions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Cell Differentiation / physiology
  • Embryo, Mammalian
  • Gene Expression Regulation, Developmental / genetics
  • Green Fluorescent Proteins
  • Intermediate Filament Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Models, Biological
  • Nerve Degeneration / genetics
  • Nerve Tissue Proteins / metabolism
  • Nestin
  • Neuroglia / physiology*
  • Neurons / physiology
  • Organ Culture Techniques / methods
  • Prosencephalon / cytology
  • Receptors, Notch / metabolism*
  • Signal Transduction / physiology*
  • Stem Cells / physiology*
  • Time Factors
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / physiology*


  • Intermediate Filament Proteins
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nestin
  • Receptors, Notch
  • Green Fluorescent Proteins
  • MIB1 protein, mouse
  • Ubiquitin-Protein Ligases