discs large regulates somatic cyst cell survival and expansion in Drosophila testis

Abstract

Gonad development requires a coordinated soma-germline interaction that ensures renewal and differentiation of germline and somatic stem cells to ultimately produce mature gametes. The Drosophila tumour suppressor gene discs large (dlg) encodes a septate junction protein functioning during epithelial polarization, asymmetric neuroblast division, and formation of neuromuscular junctions. Here, we report the role of dlg in testis development and its critical function in somatic cyst cells (SCCs). In these cells dlg is primarily required for their survival and expansion, and contributes to spermatocyte cyst differentiation. Cell death primarily occurred in SCCs at the end of spermatogonial amplification at a time when Dlg becomes restricted in wild-type (wt) testes to the distal somatic cells capping the growing spermatocyte cysts. RNAi depletion of dlg transcripts in early SCCs fully prevented testis development, whereas depletion in late SCCs resulted in a breakdown of spermatocyte cyst structure and germ cell individualization. Specific dlg expression in SCCs resulted in developmental rescue of dlg mutant testes, whereas its expression in germ cells exerted no such effect. dlg overexpression in wt testes led to spermatocyte cyst expansion at the expense of spermatogonial cysts. Our data demonstrate that dlg is essentially required in SCCs for their survival, expansion, and differentiation, and for the encapsulation of the germline cells.

Refining the role of Lgl, Dlg and Scrib in Tumor Suppression and Beyond: Learning from the Old Time Classics

“…The dlg testes are extremely small, with reduced number of GSCs loosely attached to the hub ( Figure 5B, F). The Dlg protein is present in all somatic cells including the hub, SSCs and SCCs ( Figure 4A-D) and the specific requirement of dlg in these cells is further supported by the finding that the mutant phenotype is rescued by expressing dlg in somatic cells but not in germ cells (Papagiannouli and Mechler 2009). In SSCs and early SCCs dlg plays a critical role in the establishment of a normal cyst structure, whereas in spermatogonial and spermatocyte stages dlg is critical for cyst survival, growth, expansion and maintenance of the integrity of the cysts' microenvironment.…”

“…The physical contacts among the testis cell populations are critical as they allow the exchange of signals among GSCs and SSCs as well as SCCs, spermatogonial cells and spermatocytes that promote tissue survival and testis homeostasis. We have recently investigated a new role of dlg in the Drosophila testis (Papagiannouli andMechler 2009, Papagiannouli andMechler 2010). In contrast to the overgrowth phenotypes observed in imaginal discs and brain hemispheres, dlg inactivation leads to testis degeneration during early larval development.…”

Somatic gonadal cells: The supporting cast for the germline

“…Mutation of dlg results in a reduced number GSCs, spermatogonia, and late somatic cyst cells. The remaining late somatic cyst cells appear to undergo cell death and these results in the subsequent death of 8 and 16-cell cyst (Papagiannouli and Mechler, 2009). In contrast, overexpression of dlg triggers germ cell differentiation, based on the presence of more 8 and 16-cell cysts.…”

“…The septate junction protein, Discs Large (DLG), is localized to sites of germlinesoma interactions and is required for germ cell development (Papagiannouli and Mechler, 2009). DLG is observed in the hub and at junctions between GSCs and CySCs, and spermatogonia and somatic cyst cells (Papagiannouli and Mechler, 2009).…”

“…In contrast, overexpression of dlg triggers germ cell differentiation, based on the presence of more 8 and 16-cell cysts. Thus, DLG is required early for ensheathment of spermatogonia by somatic cyst cells and the establishment of junctions between these cells, which is required for survival of the germline and somatic cells (Papagiannouli and Mechler, 2009).…”