PT  - JOURNAL ARTICLE
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
TI  - AUTS2 Governs Cerebellar Development, Purkinje Cell Maturation, Motor Function and Social Communication
AID  - 10.1101/2020.01.24.917989
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.01.24.917989
4099  - http://biorxiv.org/content/early/2020/01/25/2020.01.24.917989.short
4100  - http://biorxiv.org/content/early/2020/01/25/2020.01.24.917989.full
AB  - 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.