RT Journal Article
SR Electronic
T1 AUTS2 Governs Cerebellar Development, Purkinje Cell Maturation, Motor Function and Social Communication
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.24.917989
DO 10.1101/2020.01.24.917989
A1 Kunihiko Yamashiro
A1 Kei Hori
A1 Esther S.K. Lai
A1 Ryo Aoki
A1 Kazumi Shimaoka
A1 Saki F. Egusa
A1 Asami Sakamoto
A1 Manabu Abe
A1 Kenji Sakimura
A1 Takaki Watanabe
A1 Naofumi Uesaka
A1 Masanobu Kano
A1 Mikio Hoshino
YR 2020
UL http://biorxiv.org/content/early/2020/01/25/2020.01.24.917989.abstract
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.