Loss of CRMP1 and CRMP2 results in migration defects of Purkinje cells in the X lobule of the mouse cerebellum

Abstract

The three-layered structure of the mammalian cerebellar cortex is generated through the coordinated migration of cerebellar neurons. Purkinje cells migrate and form a three- to four-cell-thick aggregate below the external granule cell layer during the embryonic stage, and align to form a monocellular arrangement in the Purkinje cell layer during the postnatal period. We previously reported the involvement of Cdk5-mediated CRMP2 phosphorylation in Purkinje cell migration and the synergistic roles of two other CRMPs, CRMP1 and CRMP4. In the present study, we investigated the loss of function of CRMP2 along with the synergistic function of CRMP1 in the migration and alignment of Purkinje cells. We found deficits in the migration and alignment of Purkinje cells in lobule X of the cerebella of CRMP1 and CRMP2 double knockout mice. Because lobule X, also called the flocculonodular lobe, is involved in the maintenance of balance equilibrium and muscle tone, we conducted balance beam and grip power tests in these mice and found impaired performance on the balance beam test and lower grip power in CRMP1 and CRMP2 double knockout mice, indicating the importance of these genes in proper cerebellar development.