TAG-1-assisted progenitor elongation streamlines nuclear migration to optimize subapical crowding

Nat Neurosci. 2013 Nov;16(11):1556-66. doi: 10.1038/nn.3525. Epub 2013 Sep 22.


Neural progenitors exhibit cell cycle-dependent interkinetic nuclear migration (INM) along the apicobasal axis. Despite recent advances in understanding its underlying molecular mechanisms, the processes to which INM contributes mechanically and the regulation of INM by the apicobasally elongated morphology of progenitors remain unclear. We found that knockdown of the cell-surface molecule TAG-1 resulted in retraction of neocortical progenitors' basal processes. Highly shortened stem-like progenitors failed to undergo basalward INM and became overcrowded in the periventricular (subapical) space. Surprisingly, the overcrowded progenitors left the apical surface and migrated into basal neuronal territories. These observations, together with the results of in toto imaging and physical tests, suggest that progenitors may sense and respond to excessive mechanical stress. Although, unexpectedly, the heterotopic progenitors remained stem-like and continued to sequentially produce neurons until the late embryonic period, histogenesis was severely disrupted. Thus, INM is essential for preventing overcrowding of nuclei and their somata, thereby ensuring normal brain histogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / genetics
  • Cell Cycle / physiology*
  • Cell Membrane / metabolism
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Cell Proliferation
  • Cerebral Cortex / cytology
  • Computer Simulation
  • Contactin 2 / genetics
  • Contactin 2 / metabolism*
  • Embryo, Mammalian
  • Epithelium / embryology
  • Epithelium / physiology
  • Histones / metabolism
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mice
  • Mice, Inbred ICR
  • Mice, Transgenic
  • Models, Biological
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neural Stem Cells / physiology
  • Neural Stem Cells / ultrastructure*
  • Organ Culture Techniques
  • RNA Interference / physiology
  • RNA, Small Interfering / metabolism
  • Wnt3A Protein / genetics
  • Wnt3A Protein / metabolism


  • Cntn2 protein, mouse
  • Contactin 2
  • Histones
  • Luminescent Proteins
  • Nerve Tissue Proteins
  • RNA, Small Interfering
  • Wnt3A Protein
  • Wnt3a protein, mouse