STRA8 Shuttles between Nucleus and Cytoplasm and Displays Transcriptional Activity

Homeobox genes encode transcription factors that regulate diverse developmental events. The largest known homeobox gene clusterthe X-linked mouse reproductive homeobox (Rhox) cluster -harbors genes whose expression patterns and functions are largely unknown. Here, we report that a member of this cluster, Rhox10, is expressed in male germ cells. Rhox10 is highly transcribed in spermatogonia in vivo and is upregulated in response to the differentiation-inducing agent retinoic acid in vitro. Using a specific RHOX10 antiserum that we generated, we found that RHOX10 protein is selectively expressed in fetal gonocytes, germline stem cells, spermatogonia, and early spermatocytes. RHOX10 protein undergoes a dramatic shift in subcellular localization as germ cells progress from mitotically arrested gonocytes to mitotic spermatogonia and from mitotic spermatogonia to early meiotic spermatocytes, consistent with RHOX10 performing different functions in these stages.

Section: Discussionmentioning

confidence: 99%

Dynamic expression pattern and subcellular localization of the Rhox10 homeobox transcription factor during early germ cell development

Song¹,

Dann²,

McCarrey³

et al. 2012

“…Since then, the role of STRA8 as an essential initiator of meiosis in male and female germ cells has been clearly demonstrated in Stra8 knockout mice that were infertile, due to disrupted meiosis and premature chromosome condensation (Baltus et al 2006, Mark et al 2008. Although the exact mechanism through which STRA8 induces meiosis is not well understood, the protein has been shown to shuttle between the cytoplasm and the nucleus in different types of germ cells, and to display transcriptional activity in cell lines when it is expressed in the nucleus (Tedesco et al 2009). Several groups, including ours, have used STRA8, alongside KIT (another marker of differentiating spermatogonia), as a marker for differentiating gonocytes (Wang & Culty 2007, Zhou et al 2008b.…”

Section: Transitional Gonocyte Differentiation In Rodentsmentioning

confidence: 99%

Mammalian gonocyte and spermatogonia differentiation: recent advances and remaining challenges

Manku¹,

Culty²

2015

125

105

The production of spermatozoa relies on a pool of spermatogonial stem cells (SSCs), formed in infancy from the differentiation of their precursor cells, the gonocytes. Throughout adult life, SSCs will either self-renew or differentiate, in order to maintain a stem cell reserve while providing cells to the spermatogenic cycle. By contrast, gonocytes represent a transient and finite phase of development leading to the formation of SSCs or spermatogonia of the first spermatogenic wave. Gonocyte development involves phases of quiescence, cell proliferation, migration, and differentiation. Spermatogonia, on the other hand, remain located at the basement membrane of the seminiferous tubules throughout their successive phases of proliferation and differentiation. Apoptosis is an integral part of both developmental phases, allowing for the removal of defective cells and the maintenance of proper germ-Sertoli cell ratios. While gonocytes and spermatogonia mitosis are regulated by distinct factors, they both undergo differentiation in response to retinoic acid. In contrast to postpubertal spermatogenesis, the early steps of germ cell development have only recently attracted attention, unveiling genes and pathways regulating SSC self-renewal and proliferation. Yet, less is known on the mechanisms regulating differentiation. The processes leading from gonocytes to spermatogonia have been seldom investigated. While the formation of abnormal gonocytes or SSCs could lead to infertility, defective gonocyte differentiation might be at the origin of testicular germ cell tumors. Thus, it is important to better understand the molecular mechanisms regulating these processes. This review summarizes and compares the present knowledge on the mechanisms regulating mammalian gonocyte and spermatogonial differentiation.

“…Like Rarb (a classical RA-response gene), Stra8 is considered a type II immediate early response gene. The STRA8 protein was originally described as cytoplasmic in P19 EC cells (Oulad-Abdelghani et al 1996), but recent evidence suggests that it shuttles between nucleus and cytoplasm, and may bind DNA (Tedesco et al 2009). Differentially phosphorylated forms have been demonstrated but any significance of these has not been shown (Oulad-Abdelghani et al 1996).…”

Section: How Does Ra Work Its Magic?mentioning

confidence: 99%

Sex determination in mammalian germ cells: extrinsic versus intrinsic factors

Bowles

Koopman²

2010

107

Mammalian germ cells do not determine their sexual fate based on their XX or XY chromosomal constitution. Instead, sexual fate is dependent on the gonadal environment in which they develop. In a fetal testis, germ cells commit to the spermatogenic programme of development during fetal life, although they do not enter meiosis until puberty. In a fetal ovary, germ cells commit to oogenesis by entering prophase of meiosis I. Although it was believed previously that germ cells are pre-programmed to enter meiosis unless they are actively prevented from doing so, recent results indicate that meiosis is triggered by a signaling molecule, retinoic acid (RA). Meiosis is avoided in the fetal testis because a male-specifically expressed enzyme actively degrades RA during the critical time period. Additional extrinsic factors are likely to influence sexual fate of the germ cells, and in particular, we postulate that an additional male-specific fate-determining factor or factors is involved. The full complement of intrinsic factors that underlie the competence of gonadal germ cells to respond to RA and other extrinsic factors is yet to be defined.