ZFIN ID: ZDB-PUB-120417-1
Intralineage directional notch signaling regulates self-renewal and differentiation of asymmetrically dividing radial glia
Dong, Z., Yang, N., Yeo, S.Y., Chitnis, A., and Guo, S.
Date: 2012
Source: Neuron   74(1): 65-78 (Journal)
Registered Authors: Chitnis, Ajay, Dong, Zhiqiang, Guo, Su, Yang, Nan, Yeo, Sang-Yeob
Keywords: none
MeSH Terms:
  • Animals
  • Asymmetric Cell Division/physiology*
  • Cell Lineage
  • Cell Polarity
  • Embryo, Nonmammalian
  • Gene Expression Profiling
  • Neurogenesis/physiology
  • Neuroglia/cytology*
  • Neuroglia/physiology
  • Prosencephalon/cytology
  • Prosencephalon/embryology*
  • Receptors, Notch/metabolism*
  • Signal Transduction/physiology
  • Stem Cells/cytology*
  • Stem Cells/physiology
  • Ubiquitin-Protein Ligases/physiology
  • Zebrafish
  • Zebrafish Proteins/physiology
PubMed: 22500631 Full text @ Neuron

Asymmetric division of progenitor/stem cells generates both self-renewing and differentiating progeny and is fundamental to development and regeneration. How this process is regulated in the vertebrate brain remains incompletely understood. Here, we use time-lapse imaging to track radial glia progenitor behavior in the developing zebrafish brain. We find that asymmetric division invariably generates a basal self-renewing daughter and an apical differentiating sibling. Gene expression and genetic mosaic analysis further show that the apical daughter is the source of Notch ligand that is essential to maintain higher Notch activity in the basal daughter. Notably, establishment of this intralineage and directional Notch signaling requires the intrinsic polarity regulator Partitioning defective protein-3 (Par-3), which segregates the fate determinant Mind bomb unequally to the apical daughter, thereby restricting the self-renewal potential to the basal daughter. These findings reveal with single-cell resolution how self-renewal and differentiation become precisely segregated within asymmetrically dividing neural progenitor/stem lineages.