Brain Building: Brain Growth Tied To Cell Division In Mouse Embryos

Vangl2 (aka Strabismus in flies) is a component of the PCP (planar cell polarity) pathway that is active in a variety of tissues and organisms. Mice that lack Vangl2 have a number of neurological defects including incomplete neural tube closure and reduced brain size.

Sokol and Lake wondered how Vangl2 might influence brain development. In the cerebral cortex, neurons are born from a pool of progenitor cells, and the time of their birth determines their fate. The research duo found that Vangl2-lacking mouse embryos had large numbers of early-born neurons and few remaining progenitor cells. This hinted that Vangl2-lacking neurons were differentiating prematurely—a suspicion confirmed in vitro.

The progenitor pool is maintained by asymmetrical division—one daughter cell becomes a neuron, the other self-renews. This fate asymmetry is thought to depend on the orientation of cell division, and the authors observed an increase in the number of symmetrically dividing progenitors in the brains of Vangl2-lacking mouse embryos. Also, Vangl2-lacking cells in culture showed symmetrical distribution of a spindle-orienting factor that in normal cells distributes asymmetrically.

Such similarities between Vangl2-lacking cells in vitro and in vivo will facilitate ongoing studies of the PCP pathway in neurogenesis.

Journal reference: Lake, B.B., and S.Y. Sokol. 2009. J. Cell Biol. doi:10.1083/jcb.200807073