Abstract
SOX3 is a transcription factor expressed within the developing and adult nervous system where it mostly functions to help maintain neural precursors. Sox3 is also expressed in other locations, notably within the spermatogonial stem/progenitor cell population in postnatal testis. Independent studies have shown that Sox3 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 Sox3 is expressed within the committed progenitor fraction of the undifferentiated spermatogonial pool. Additionally, we use a Sox3 null mouse model to define a potential role for this factor in progenitor cell function. We demonstrate that Sox3 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 Ngn3 promoter region in vivo, indicating that Ngn3 is a direct target of SOX3. Together these studies indicate that SOX3 functions as a pro-commitment factor in spermatogonial stem/progenitor cells.
Highlights
SOX3 is a transcription factor expressed within the developing and adult nervous system where it mostly functions to help maintain neural precursors
Through use of a SOX3-specific antibody[4], we confirmed by immunofluorescence (IF) analysis that SOX3 protein is restricted to spermatogonia of wild type (WT) adult testis (Fig. 1A)
Spermatogonia expressing Sox[3] displayed low levels of Cyclin D1 (Ccnd1), a marker predominantly expressed by differentiating spermatogonia (Fig. 1A)[29,30]
Summary
SOX3 is a transcription factor expressed within the developing and adult nervous system where it mostly functions to help maintain neural precursors. Using chromatin immunoprecipitation, we demonstrate that SOX3 binds to a highly conserved region in the Ngn[3] promoter region in vivo, indicating that Ngn[3] is a direct target of SOX3 Together these studies indicate that SOX3 functions as a pro-commitment factor in spermatogonial stem/progenitor cells. NGN3 + Aal cells occasionally fragment to shorter chains plus As cells and may revert gene expression patterns to a GFRα1+ state, demonstrating the dynamic nature of the stem cell pool[16,21]. This limited contribution of NGN3 + cells to the steady-state self-renewing pool is enhanced under conditions of tissue regeneration[19]. Despite the importance of such factors and pathways in fate transitions within the undifferentiated pool, the relevant downstream effectors remain poorly characterised
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