Transcriptional regulation of neonatal neural stem cells is a determinant of social behavior
Hiramoto, T.; Boku, S.; Kang, G.; Abe, S.; Barbachan e Silva, M.; Tanigaki, K.; Nagashima, M.; Ye, K.; Yamauchi, T.; Michurina, T. V.; O Broin, P.; Enikolopov, G.; Hiroi, N.
Show abstract
Rare gene variants confer a high level of penetrance to neurodevelopmental disorders, but their developmental origin and cellular substrates remain poorly understood. To address this limitation, we explored the role of TBX1, a gene encoded in a rare copy number variant, in cell and mouse models. Here, we report that neonatal Tbx1 deficiency contributes to defective peripubertal social behavior and impairs the proliferation of neonatal neural stem/progenitor cells. Moreover, TBX1 transcriptionally regulates genes linked to post-embryonic neurogenesis and neurodevelopmental disorders associated with other rare gene variants. Our data indicate a precise time window and cell type through which the social dimension is altered by a gene encoded in a rare CNV and provide a potential common mechanistic basis for a group of neurodevelopmental disorders. One-Sentence SummaryTbx1, a gene affecting neonatal stem cell proliferation, influences peripubertal social behavior.
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