PQBP1 regulates striatum development through balancing striatal progenitor proliferation and differentiation

The balance between cell proliferation and differentiation is essential for maintaining the neural progenitor pool and brain development. Although the mechanisms underlying cell proliferation and differentiation at the transcriptional level have been studied intensively, post-transcriptional regulation of cell proliferation and differentiation remains largely unclear. Here, we show that deletion of the alternative splicing regulator PQBP1 in striatal progenitors results in defective striatal development due to impaired neurogenesis of spiny projection neurons (SPNs). Pqbp1-deficient striatal progenitors exhibit declined proliferation and increased differentiation, resulting in a reduced striatal progenitor pool. We further reveal that PQBP1 associates with components in splicing machinery. The alternative splicing profiles identify that PQBP1 promotes the exon 9 inclusion of Numb, a variant that mediates progenitor proliferation. These findings identify PQBP1 as a regulator in balancing striatal progenitor proliferation and differentiation and provide alternative insights into the pathogenic mechanisms underlying Renpenning syndrome. [Display omitted] •Ablation of PQBP1 causes reduced striatal progenitor pool and impaired neurogenesis•Depletion of PQBP1 leads to declined IP proliferation and increased differentiation•PQBP1 associates with components in splicing machinery•PQBP1 modulates the alternative splicing of Numb to regulate striatum development The balance between cell proliferation and differentiation is essential for maintaining the neural progenitor pool and brain development. Liu et al. show that PQBP1 is highly expressed in striatal progenitors and mediates Numb exon 9 inclusion to balance striatal progenitors’ proliferation and differentiation.