Oral Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2013

The Snail family of transcriptional repressors - conserved regulators of spermatogenesis (#2)

Gary Hime 1 , Aviv Gafni 1 , Arjun Chahal 1 , Agnes Gany 1 , Franca Casagranda 1 , Helen Abud 2
  1. Anatomy and Physiology, University of Melbourne, Parkville, Vic, Australia
  2. Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia

A number of regenerative tissues in Drosophila, including gonads from both adult males and females, are dependent upon stem cells for renewal. Male Drosophila produce sperm from a pair of testes, each comprising a coiled tube with a closed apical end and a basal end that connects to a seminal vesicle. Mitotically active cells are restricted to the apical testis where the stem cell niche responsible for regeneration of germline stem cells (GSCs) is located. 8-10 GSCs surround a group of somatic niche cells termed the hub. Mitotic division of a GSC results in a daughter remaining attached to the hub that maintains GSC identity and a daughter displaced from the hub that becomes a gonialblast, or primary spermatogonial cell. The gonialblast undergoes four more rounds of mitosis characterised by incomplete cytokinesis to produce a cyst of 16 interconnected spermatogonia which then proceed through pre-meiotic S-phase and differentiate as spermatocytes. The ease of genetic analysis in Drosophila has allowed identification of molecules required both within stem cells and in neighbouring niche cells. We have identified that Snail family proteins are required for maintenance of germline stem cells in the adult Drosophila testis. Snail proteins are zinc-finger DNA-binding proteins that act as transcriptional repressors at E-box sequences in target gene promoters. Three Snail members are present in Drosophila (Snail, Escargot & Worniu) and mouse/human (Snai1/Snail, Snai2/Slug & Snai3/Smuc). Snail proteins play key, conserved roles in triggering epithelial to mesenchymal transitions (EMT) in both physiological and pathological situations. Snail proteins are also expressed in various stem cell populations in both Drosophila and vertebrates. Escargot is highly expressed in undifferentiated spermatogonia and somatic stem cells in the Drosophila testis but loss of Escargot function specifically affects the somatic component of the testis. Although loss of Escargot has no effect in germ cells, mutation of the Snail paralog results in loss of germline stem cells from the testis niche. Conditional loss of Snai1 in the mouse testis does not appear to result in a testicular defect but loss of Snai2 causes severe disruptions to spermatogenesis.