Ptbp2 Controls an Alternative Splicing Network Required for Cell Communication during Spermatogenesis

Abstract

Summary: Alternative splicing has essential roles in development. Remarkably, spermatogenic cells express more alternatively spliced RNAs compared to most whole tissues; however, regulation of these RNAs remains unclear. Here, we characterize the alternative splicing landscape during spermatogenesis and reveal an essential function for the RNA-binding protein Ptbp2 in this highly regulated developmental program. We found that Ptbp2 controls a network of genes involved in cell adhesion, migration, and polarity, suggesting that splicing regulation by Ptbp2 is critical for germ cell communication with Sertoli cells (multifunctional somatic cells necessary for spermatogenesis). Indeed, Ptbp2 ablation in germ cells resulted in disorganization of the filamentous actin (F-actin) cytoskeleton in Sertoli cells, indicating that alternative splicing regulation is necessary for cellular crosstalk during germ cell development. Collectively, the data delineate an alternative splicing regulatory network essential for spermatogenesis, the splicing factor that controls it, and its biological importance in germ-Sertoli communication. : Hannigan et al. characterize the alternative splicing landscape during spermatogenesis and reveal an essential role for Ptbp2 in this temporal regulation. Moreover, splicing regulation by Ptbp2 is required for proper regulation of trafficking and cell polarity genes and cell communication during germ cell development. Keywords: post-transcriptional regulation, spermatogenesis, cell-cell communication, alternative splicing, RNA networks