Transcriptional Regulation of Spermatogonial Progenitor Development and Meiotic Entry.

Abstract

TAF4b is a component of the general transcription factor complex TFIID that is required for oogenesis and long-term spermatogenesis in the mouse. Male mice that lack TAF4b complete several rounds of early spermatogenesis, but fail to maintain it throughout adult life. In mammals, the ability to maintain spermatogenesis is largely the function of spermatogonial stem cells (SSCs) and their associated niche that provides continuous production of spermatogenic progenitors throughout most of adult life. Successful germ cell transplantation assays into adult TAF4b-deficient host testes previously demonstrated that TAF4b is apparently dispensable for providing essential components of the adult SSC niche. Here, we begin to test whether TAF4b regulates a germ cell-autonomous program of gene transcription required for the development of self-renewing SSCs in early postnatal life required for full spermatogenic maintenance in the adult. To examine the potential disruption of SSC development, we have compared SSC gene expression signatures in the wild type versus the TAF4b-deficient early postnatal testis. This analysis has revealed a reduction in several key components of the SSC transcriptome including Stra8, Lin28, Mvh and Gfra1. To more precisely examine the SSC compartment, we have enriched for SSCs using Thy1-sorting of the early postnatal testis that similarly revealed gene expression signatures consistent with a reduction in SSC renewal. Most importantly, we have revealed a lag in meiotic entry in the TAF4b-deficient testis that may provide a link between timely establishment of the self-renewing SSCs and their subsequent entry into meiosis. A model of how TAF4b may regulate these distinct processes in spermatogenesis will be presented. (platform)