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

¹ Department of Biophysics, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
² CREST, Japan Science and Technology Corporation, Kawaguchi 332-0012, Japan
³ Department of Anatomy, Shimane Medical University, Izumo 693-8501
⁴ Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto 606-8315
⁵ TOREST, Japan Science and Technology Corporation, Kawaguchi 332-0012, Japan
⁶ Department of Developmental Neurobiology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
^* Author for correspondence (e-mail: kengaku{at}nb.biophys.kyoto-u.ac.jp

Accepted 14 May 2001

The molecular mechanisms that govern the coordinated programs of axonogenesis and cell body migration of the cerebellar granule cell are not well understood. In Pax6 mutant rats (rSey²/rSey²), granule cells in the external germinal layer (EGL) fail to form parallel fiber axons and to migrate tangentially along these fibers despite normal expression of differentiation markers. In culture, mutant cells sprout multiple neurites with enlarged growth cones, suggesting that the absence of Pax6 function perturbs cytoskeletal organization. Some of these alterations are cell-autonomous and rescuable by ectopic expression of Pax6 but not by co-culture with wild-type EGL cells. Cell-autonomous control of cytoskeletal dynamics by Pax6 is independent of the ROCK-mediated Rho small GTPase pathway. We propose that in addition to its roles during early patterning of the CNS, Pax6 is involved in a novel regulatory step of cytoskeletal organization during polarization and migration of CNS neurons.

Key words: Pax6, Cerebellum, Cell polarization, Granule cell, Parallel fiber, Cytoskeleton

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