Mechanism of microcephaly development by the deletion of transcriptional regulator

AUTS2 syndrome patients often exhibit microcephaly, yet its etiological mechanism remains unclear. 

The researchers developed a mouse model mutated for Auts2 that recapitulates the AUTS2 syndrome-associated microcephaly.

They show that AUTS2 collaborates with Polycomb complex PRC2 in intermediate progenitor cells (IPCs) to promote H3K27 trimethylation and suppress the expression of target genes. The authors also demonstrate that AUTS2 promotes IPC division and production of upper-layer neurons by suppressing Robo1 expression.

Loss of Auts2 results in increased Robo1 expression, lower levels of IPC division, and decreased neuron production, leading to microcephaly.

https://www.embopress.org/doi/full/10.1038/s44318-024-00343-7

https://sciencemission.com/microcephaly-associated-transcriptional-regulator-AUTS2