Dlic1 deletion impaired cerebellar development in mouse

Abstract

The cerebellum is an important model system to study Central Nervous System, it has a striking morphology consisting of folia separated by fissures of different lengths, and the molecules controlling the process of cerebellar development have been unclear. In this study, we report an unrecognized contribution of Dlic1 to the postnatal development of murine cerebellum. Dlic1 encodes a light intermediate chain of cytoplasmic dynein 1, it is a subunit unique to the cytoplasmic form of dynein, and how it contributes to dynein function is not fully understood. Our data show that Dlic1 deletion leads to impaired cerebellar development, foliation and fissuration, the volume of the cerebellum was evidently reduced. Consistent with the histological defects, Dlic1 knockout mice show defective motor coordination, this strongly indicates the fundamental role of Dlic1 in cerebellar development and function. Purkinje cells are located within the cerebellum and form synapses with granule cells. In Dlic1-/- mice, Purkinje cells display reduced dendritic complexity and the distribution of dynein in Purkinje cell layer is changed. We also found that Dlic1 deletion reduced the protein levels of dynein subunits and leads to the defective assembling of dynein subunits. These data indicate that Dlic1 may affect cerebellar development through affecting the normal function of dynein.\n\nAbbreviations