Pax6 regulates granule cell polarization during parallel fiber formation in the developing cerebellum

The molecular mechanisms that govern the coordinated programs of axonogenes is and cell body migration of the cerebellar granule cell are not well unde rstood. In Pax6 mutant rats (rSey(2)/rSey(2)), granule cells in the externa l germinal layer (EGL) fail to form parallel fiber axons and to migrate tan gentially along these fibers despite normal expression of differentiation m arkers. In culture, mutant cells sprout multiple neurites with enlarged gro wth cones, suggesting that the absence of Pax6 function perturbs cytoskelet al organization. Some of these alterations are cell-autonomous and rescuabl e by ectopic expression of Pax6 but not by co-culture with wild-type EGL ce lls. Cell-autonomous control of cytoskeletal dynamics by Pax6 is independen t of the ROCK-mediated Rho small GTPase pathway. We propose that in additio n to its roles during early patterning of the CNS, Pax6 is involved in a no vel regulatory step of cytoskeletal organization during polarization and mi gration of CNS neurons.