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 resulted in defective striatal development due to  impaired neurogenesis of spiny projection neurons (SPNs). Pqbp1 deficiency 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 novel regulator in balancing striatal progenitor  proliferation and differentiation and provide alternative insights into the pathogenic  mechanisms underlying Renpenning syndrome. Overall design: Total RNA from the Isolating the strong GFP-positive striatal IPs at E15.5  Pqbp1+/Y;Dlx5/6-Cre-IRES-EGFP and Pqbp1fl/Y;Dlx5/6-Cre-IRES-EGFP mice by using fluorescence-activated cell sorting (FACS) extracted for deep sequencing, in triplicate, using Illumina HiSeq X Ten.