Autism risk genes converge on PBX1 to govern neural cell growth
Fu, S.; Wynshaw-Boris, A.
Show abstract
The alteration of neural progenitor cell (NPC) proliferation underlies autism spectrum disorders (ASD). It remains unclear whether targeting convergent downstream targets among mutations from different genes and individuals can rescue this alteration. We identified PBX1 as a convergent target of three autism risk genes: CTNNB1, PTEN, and DVL3, using isogenic iPSC-derived 2D NPCs. Overexpression of the PBX1a isoform effectively rescued increased NPC proliferation in all three isogenic ASD-related variants. Dysregulation of PBX1 in NPCs was further confirmed in publicly available datasets from other models of ASD. These findings spotlight PBX1, known to play important roles during olfactory bulb/adult neurogenesis and in multiple cancers, as an unexpected and key downstream target, influencing NPC proliferation in ASD and neurodevelopmental syndromes.
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