TY - JOUR T1 - AUTS2 Governs Cerebellar Development, Purkinje Cell Maturation, Motor Function and Social Communication JF - bioRxiv DO - 10.1101/2020.01.24.917989 SP - 2020.01.24.917989 AU - Kunihiko Yamashiro AU - Kei Hori AU - Esther S.K. Lai AU - Ryo Aoki AU - Kazumi Shimaoka AU - Saki F. Egusa AU - Asami Sakamoto AU - Manabu Abe AU - Kenji Sakimura AU - Takaki Watanabe AU - Naofumi Uesaka AU - Masanobu Kano AU - Mikio Hoshino Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/01/25/2020.01.24.917989.abstract N2 - Autism susceptibility candidate 2 (AUTS2), a risk gene for autism spectrum disorders (ASDs), is implicated in telencephalon development. Because AUTS2 is also expressed in the cerebellum where defects have been linked to ASDs, we investigated AUTS2 functions in the cerebellum. AUTS2 is specifically localized in Purkinje cells (PCs) and Golgi cells during postnatal development. Auts2 conditional knockout (cKO) mice exhibited smaller and deformed cerebella containing immature-shaped PCs with reduced expression of Cacna1a. Auts2 cKO and knock-down experiments implicated AUTS2 participation in elimination and translocation of climbing fiber synapses, and restriction of parallel fiber synapse numbers. Auts2 cKO mice exhibited behavioral impairments in motor learning and vocal communications. Because Cacna1a is known to regulate synapse development in PCs, it suggests that AUTS2 is required for PC maturation to elicit normal development of PC synapses and thus the impairment of AUTS2 may cause cerebellar dysfunction related to psychiatric illnesses such as ASDs. ER -