TY - JOUR
T1 - Zbtb16 regulates social cognitive behaviors and neocortical development
AU - Usui, Noriyoshi
AU - Berto, Stefano
AU - Konishi, Ami
AU - Kondo, Makoto
AU - Konopka, Genevieve
AU - Matsuzaki, Hideo
AU - Shimada, Shoichi
N1 - Funding Information:
We thank Yoko Sasaki, Ryoko Aramaki, Yuta Ono, Yuuto Ohara, Yuuki Takaba, Xie Min-Jue, and Tomoko Taniguchi for their support. This work was supported by the Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research (C) (20K06872) to N.U.; JSPS Grant-in-Aid for Early-Career Scientists (18K14814) to N.U.; Takeda Science Foundation to N.U.; SENSHIN Medical Research Foundation to N.U.; The Osaka Medical Research Foundation for Intractable Diseases to N.U.; Public Health Science Foundation to N.U.; Eli Lilly Japan Research Grant to N.U.; the Grant for Life Cycle Medicine from Faculty of Medical Sciences, the University of Fukui to N.U.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/6
Y1 - 2021/6
N2 - Zinc finger and BTB domain containing 16 (ZBTB16) play the roles in the neural progenitor cell proliferation and neuronal differentiation during development, however, how the function of ZBTB16 is involved in brain function and behaviors unknown. Here we show the deletion of Zbtb16 in mice leads to social impairment, repetitive behaviors, risk-taking behaviors, and cognitive impairment. To elucidate the mechanism underlying the behavioral phenotypes, we conducted histological analyses and observed impairments in thinning of neocortical layer 6 (L6) and a reduction of TBR1+ neurons in Zbtb16 KO mice. Furthermore, we found increased dendritic spines and microglia, as well as developmental defects in oligodendrocytes and neocortical myelination in the prefrontal cortex (PFC) of Zbtb16 KO mice. Using genomics approaches, we identified the Zbtb16 transcriptome that includes genes involved in neocortical maturation such as neurogenesis and myelination, and both autism spectrum disorder (ASD) and schizophrenia (SCZ) pathobiology. Co-expression networks further identified Zbtb16-correlated modules that are unique to ASD or SCZ, respectively. Our study provides insight into the novel roles of ZBTB16 in behaviors and neocortical development related to the disorders.
AB - Zinc finger and BTB domain containing 16 (ZBTB16) play the roles in the neural progenitor cell proliferation and neuronal differentiation during development, however, how the function of ZBTB16 is involved in brain function and behaviors unknown. Here we show the deletion of Zbtb16 in mice leads to social impairment, repetitive behaviors, risk-taking behaviors, and cognitive impairment. To elucidate the mechanism underlying the behavioral phenotypes, we conducted histological analyses and observed impairments in thinning of neocortical layer 6 (L6) and a reduction of TBR1+ neurons in Zbtb16 KO mice. Furthermore, we found increased dendritic spines and microglia, as well as developmental defects in oligodendrocytes and neocortical myelination in the prefrontal cortex (PFC) of Zbtb16 KO mice. Using genomics approaches, we identified the Zbtb16 transcriptome that includes genes involved in neocortical maturation such as neurogenesis and myelination, and both autism spectrum disorder (ASD) and schizophrenia (SCZ) pathobiology. Co-expression networks further identified Zbtb16-correlated modules that are unique to ASD or SCZ, respectively. Our study provides insight into the novel roles of ZBTB16 in behaviors and neocortical development related to the disorders.
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U2 - 10.1038/s41398-021-01358-y
DO - 10.1038/s41398-021-01358-y
M3 - Article
C2 - 33895774
AN - SCOPUS:85104873730
SN - 2158-3188
VL - 11
JO - Translational Psychiatry
JF - Translational Psychiatry
IS - 1
M1 - 242
ER -