Ptbp2 controls an alternative splicing network required for cell communication during spermatogenesis [HITS-CLIP]. Mus musculus

Alternative splicing (AS) plays key roles in the specialization of cell functions in different tissues and stages of development. In spermatogenic cells, the complexity of AS isoforms exceeds that of most whole tissues, but the regulation, dynamics, and functions of AS in spermatogenesis have remained poorly defined. We previously demonstrated that the RNA binding protein Ptbp2 is essential for cell survival during spermatogenesis; however, the underlying mechanisms were not explored. Here, we demonstrate that Ptbp2 is a critical AS regulator in spermatogenic cells, and controls a functionally-related network of genes involved in germ cell adhesion and protein trafficking to and from the plasma membrane. In parallel, we identify distinct AS programs in different stages of spermatogenesis, and demonstrate an important role for Ptbp2 in stage-specific AS regulation. Collectively, the data provide new insights into the temporal dynamics and importance of AS in mammalian germ cell development, and demonstrate a central role for Ptbp2 in its regulation. Overall design: Three Ptbp2 HITS-CLIP libraries generated from 8 week old CD1 mouse testes (3 biologic replicate animals).