Soma-Germline communication and coordination in Drosophila spermatogenesis: understanding the role of cortical polarity proteins Dlg, Lgl and Scrib in testis homeostasis

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A fundamental question in biology is how cell-cell communication and exchange of short-range signals from the local tissue microenvironment regulates cell proliferation and cell fate for setting up functional tissues. In all adult tissues harboring stem cells, tissue homeostasis and repair relies on the proper communication of stem cells and of their differentiating daughter cells with the local tissue microenvironment. The Drosophila testis provides an excellent system to study in vivo how closely apposed cell types reciprocally communicate to coordinate their co-differentiation, since the somatic cyst stem cells and their daughter somatic cyst cells (collectively called cyst cells) encapsulate the germ cells creating a cyst microenvironment. So far, it remains a mystery how these tightly packed cysts coordinate cortical polarity and cell shape changes with membrane addition, cellular trafficking and signaling at their contact sites, and there is no mechanism describing how cyst cells in Drosophila testis grow, elongate and ensheath the germ cells in various stages of differentiation. My new preliminary data suggest that cyst cells are crucially important for soma-germline cyst integrity and a functional cyst microenvironment is a prerequisite for cyst cell-germline coordination in terms of signaling exchange and co-differentiation. Primary candidates for this intimate interaction are Dlg, Scrib and Lgl, highly conserved polarity and scaffolding proteins that localize at the cortical side of the testis cyst cells and control testicular cyst integrity. The immediate next challenges are to: (1) elucidate cyst cell polarity and architecture, (2) investigate the role of Dlg in cyst cell function and cyst cell-germline coordination, by characterizing the Dlg phenotype and protein dynamics, and by mapping the functional role of the Dlg protein domains, and (3) investigate how and to what extend Dlg collaborates with Lgl and Scrib to promote cyst cell polarity and function. Systematic analysis of Dlg, Scrib and Lgl function will elucidate not only cyst cell architecture, but most importantly will identify key gene products and mechanisms involved in local cyst cell-germline communication. Using well-established genetic tools, cell-type specific markers and high-resolution imaging techniques we can manipulate cell function in a spatio-temporal controlled way within the soma-germline microenvironment to decode how signal transmission, membrane trafficking, cell morphological changes and polarity are established, maintained and coordinated. Elucidating the mechanisms and factors that regulate polarity and soma-germline communication will uncover molecular paradigms for regulatory strategies relevant in other tissues and stem cell systems, and will eventually advance our ability to access the power of stem cells in therapeutic applications.