PAR-1 promotes primary neurogenesis and asymmetric cell divisions via control of spindle orientation

Development. 2010 Aug 1;137(15):2501-5. doi: 10.1242/dev.049833. Epub 2010 Jun 23.

Abstract

In both invertebrate and vertebrate embryonic central nervous systems, deep cells differentiate while superficial (ventricular) epithelial cells remain in a proliferative, stem cell state. The conserved polarity protein PAR-1, which is basolaterally localised in epithelia, promotes and is required for differentiating deep layer cell types, including ciliated cells and neurons. It has recently been shown that atypical protein kinase C (aPKC), which is apically enriched, inhibits neurogenesis and acts as a nuclear determinant, raising the question of how PAR-1 antagonises aPKC activity to promote neurogenesis. Here we show that PAR-1 stimulates the generation of deep cell progeny from the superficial epithelium of the neural plate and that these deep cells have a corresponding (i.e. deep cell) neuronal phenotype. We further show that gain- and loss-of-function of PAR-1 increase and decrease, respectively, the proportion of epithelial mitotic spindles with a vertical orientation, thereby respectively increasing and decreasing the number of cleavages that generate deep daughter cells. PAR-1 is therefore a crucial regulator of the balance between symmetric (two superficial daughters) and asymmetric (one superficial and one deep daughter) cell divisions. Vertebrate PAR-1 thus antagonises the anti-neurogenic influence of apical aPKC by physically partitioning cells away from it in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Division
  • Developmental Biology / methods
  • Gene Expression Regulation, Developmental*
  • Green Fluorescent Proteins / metabolism
  • Microscopy, Fluorescence / methods
  • Models, Biological
  • Neural Plate / metabolism
  • Neurogenesis*
  • Protein Kinase C / metabolism
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / physiology*
  • Spindle Apparatus*
  • Time Factors
  • Xenopus Proteins / genetics
  • Xenopus Proteins / physiology*
  • Xenopus laevis

Substances

  • Xenopus Proteins
  • Green Fluorescent Proteins
  • MARK3 protein, Xenopus
  • Protein Serine-Threonine Kinases
  • PKC-3 protein
  • Protein Kinase C