During male gametogenesis, a developmentally regulated and cell type-specific transcriptional programme is activated in primary spermatocytes to prepare for differentiation of sperm. The Drosophila aly-class meiotic-arrest loci (aly, comr, achi/vis and topi) are essential for activation of transcription of many differentiation-specific genes, and several genes important for meiotic cell cycle progression, thus linking meiotic divisions to cellular differentiation during spermatogenesis. Protein interaction studies suggest that the aly-class gene products form a chromatin-associated complex in primary spermatocytes. We identify, clone and characterise a new aly-class meiotic-arrest gene, tombola (tomb), which encodes a testis-specific CXC-domain protein that interacts with Aly. The tomb mutant phenotype is more like that of aly and comr mutants than that of achi/vis or topi mutants in terms of target gene profile and chromosome morphology. tomb encodes a chromatin-associated protein required for localisation of Aly and Comr, but not Topi, to chromatin Reciprocally, aly and comr, but not topi or achi/vis, are required to maintain the normal localisation of Tomb. tomb and aly might be components of a complex paralogous to the Drosophila dREAM/Myb-MuvB and C. elegans DRM transcriptional regulatory complexes.

The extracellular matrix surrounding vertebrate oocytes is called the zona pellucida in mammals and perivitelline membrane (pvm) in birds. We have analyzed this structure in chicken follicles and laid eggs and have identified a 95-kDa component of the pvm, which, by protein sequencing, shows homology to mammalian zona pellucida proteins. Surprisingly, we could not detect this protein in ovarian granulosa cells or oocytes, but instead found high levels in the liver of the laying hen. In contrast, it is absent in rooster liver, but can be efficiently induced by estrogen treatment of the animal. An immunoscreen of a liver λ-ZAP library yielded a cDNA coding for a protein of 934 amino acids. It displayed significant homology to members of the ZP1/ZPB family from other species, notably to mouse and rat ZP1, and was therefore designated chkZP1. It is clearly different from a protein designated chkZPB that had been deposited in the database previously. Alignment of the known members of the ZP1/ZPB family demonstrated the existence of at least three subgroups, with representatives of both the ZP1 and the ZPB sequence homology group occurring in vertebrates. Northern blot analysis of liver extracts revealed the presence of a single 3.2 kb mRNA coding for chkZP1, distinct from the chkZPB transcript detectable in follicles. Immunohistochemical analysis of follicle sections demonstrates that chkZP1 can be found in the blood vessels of the theca cell layer as well as in the pvm surrounding the oocyte. Thus, in the chicken, at least one of the major pvm components is synthesized in the liver, and is transported via the bloodstream to the follicle.2 by guest on

Sexual reproduction depends on the production of haploid gametes, and their fusion to form diploid zygotes. Here, we discuss sperm production and function in a molecular and functional evolutionary context, drawing predominantly from studies in model organisms (mice, Drosophila, Caenorhabditis elegans). We consider the mechanisms involved in establishing and maintaining a germline stem cell population in testes, as well as the factors that regulate their contribution to the pool of differentiating cells. These processes involve considerable interaction between the germline and the soma, and we focus on regulatory signalling events in a variety of organisms. The male germline has a unique transcriptional profile, including expression of many testis-specific genes. The evolutionary pressures associated with gene duplication and acquisition of testis function are discussed in the context of genome organization and transcriptional regulation. Post-meiotic differentiation of spermatids involves very dramatic changes in cell shape and acquisition of highly specialized features. We discuss the variety of sperm motility mechanisms and how various reproductive strategies are associated with the diversity of sperm forms found in animals.

SummaryAppropriate regulation of signal transduction pathways is essential for normal development and is often disrupted in disease. Therefore, many regulatory mechanisms and feedback loops have evolved to ensure appropriate signalling. One mechanism previously suggested to modulate a range of signal transduction pathways involves the internalisation and destruction of transmembrane receptors by the endocytic trafficking machinery. Strikingly, a recent report has suggested that the endocytic trafficking of the Drosophila JAK-STAT pathway receptor Domeless (Dome) does not act to downregulate pathway activity, but rather is necessary for in vivo signalling. Here, we examine this relationship to address the interaction of Drosophila JAK-STAT pathway signalling and endocytic trafficking. We show that Dome is trafficked through clathrin-mediated endocytosis and a directed RNAi screen identified several components of the endocytic machinery as negative regulators of pathway signalling. We demonstrate that Dome signals both from the plasma membrane and internalised vesicles and show, using knockdown experiments, that endocytic components negatively regulate JAK-STAT signalling in vivo. As such, disruption in endocytic trafficking represents a potent negative regulator of the disease relevant JAK-STAT signalling cascade.

JAK-STAT signaling is a highly conserved regulator of stem cells and their niches. Aberrant activation in hematopoietic stem cells is the underlying cause of a majority of myeloproliferative diseases. This review will focus on the roles of JAK-STAT activity in three different adult stem cell systems in Drosophila. Tightly controlled levels of JAK-STAT signaling are required for stem cell maintenance and self-renewal, as hyperactivation of the pathway is associated with stem cell overproliferation. JAK-STAT activity is further essential for anchoring the stem cells in their respective niches by regulating different adhesion molecules.