Neuronal (bi)polarity as a self-organized process

SILVIA A. MENCHÓN

Seminario; Departamental seminar (Department of Human Genetics); 2011

VIB - KULeuven

Neurons are among the cell types with the most prominent asymmetry. The correct establishment of polarized domains in neurons enables their directional migration and polarized axon-dendrite formation and is thus one of the most critical steps in brain development. Neuronal polarization starts with the selection of the site from which the first neurite will grow before morphological changes are evident. It has been shown that the second neurite forms opposite to the first, not randomly. This has important consequences for neuronal development, since like that initial polarity axis determines the axis of migration and defines axonal and dendritic domains. However, it is not clear whether the formation of the second neurite also requires ?external? triggering mechanisms or is the consequence of a ?passive? mechanism, derived from the first one.To test this hypothesis we proposed a mathematical model that was based in those proposed by Altschuler et al. (Nature 2008) and Turing (Philos. T. R. Soc. B 1952). Our model assumes an activator-inhibitor dynamics and diffusion-driven instabilities. Extensive analises on the equilibriumpoints and phase and bifurcation diagrams were done, allowing us to study spontaneous symmetry breaking. As a very novel idea, we also included the effect of membrane growing and studied how polarity domains are affected by it. To experimentally validate predictions of our model we compared results of our simulations with intensity distributions of Sec8. Sec8 is a exocyst subunit localized in multiple endocytic compartments. Its intensity is a measure of endocytic and exocytic traffic which is correlated with protein accumulation on the plasma membrane due to dynamic maintenance.