Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.
Department of Child Development, United Graduate School of Child Development, Osaka University, Osaka, 565-0871, Japan.
Transl Psychiatry. 2021 Apr 24;11(1):242. doi: 10.1038/s41398-021-01358-y.
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.
锌指和 BTB 结构域蛋白 16（ZBTB16）在发育过程中的神经祖细胞增殖和神经元分化中发挥作用，然而，ZBTB16 的功能如何参与大脑功能和行为尚不清楚。在这里，我们展示了小鼠中 Zbtb16 的缺失导致社交障碍、重复行为、冒险行为和认知障碍。为了阐明这些行为表型的机制，我们进行了组织学分析，观察到 Zbtb16 KO 小鼠的新皮层 6 层（L6）变薄和 TBR1+神经元减少。此外，我们发现 Zbtb16 KO 小鼠的前额叶皮层（PFC）中树突棘和小胶质细胞增多，少突胶质细胞和皮质髓鞘发育缺陷。通过基因组学方法，我们鉴定了包含与神经发生和髓鞘形成等新皮层成熟相关基因的 Zbtb16 转录组，这些基因与自闭症谱系障碍（ASD）和精神分裂症（SCZ）的病理生理学有关。共表达网络进一步鉴定了分别与 ASD 或 SCZ 相关的独特的 Zbtb16 相关模块。我们的研究为 ZBTB16 在与疾病相关的行为和新皮层发育中的新作用提供了深入了解。
