SOX3 promotes generation of committed spermatogonia in postnatal mouse testes

Abstract

<p>SOX3 is a transcription factor expressed within the developing and adult nervous system where it mostly functions to help maintain neural precursors. <i>Sox3</i> is also expressed in other locations, notably within the spermatogonial stem/progenitor cell population in postnatal testis. Independent studies have shown that <i>Sox3</i> null mice exhibit a spermatogenic block as young adults, the mechanism of which remains poorly understood. Using a panel of spermatogonial cell marker genes, we demonstrate that <i>Sox3</i> is expressed within the committed progenitor fraction of the undifferentiated spermatogonial pool. Additionally, we use a <i>Sox3</i> null mouse model to define a potential role for this factor in progenitor cell function. We demonstrate that <i>Sox3</i> expression is required for transition of undifferentiated cells from a GFRα1+ self-renewing state to the NGN3 + transit-amplifying compartment. Critically, using chromatin immunoprecipitation, we demonstrate that SOX3 binds to a highly conserved region in the <i>Ngn3</i> promoter region <i>in vivo</i>, indicating that <i>Ngn3</i> is a direct target of SOX3. Together these studies indicate that SOX3 functions as a pro-commitment factor in spermatogonial stem/progenitor cells.</p>