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Drosophila Cara Mitad (Cmi, also known as Lpt) is the N-terminal homolog of mammalian Mixed Lineage Leukemia 2 (MLL2/ALR), a core component of COMPASS-like nuclear receptor coactivator complexes. Cmi is required for the activation of ecdysone hormone targets and plays a critical role in development and tissue patterning. Using multiple approaches that include genetic interaction tests and tissue specific knockdown and overexpression of cmi, we demonstrate that Cmi has important functions in controlling wing vein patterning through regulation of the conserved Decapentaplegic (Dpp) signaling pathway. The loss of function allele, cmi1, enhances loss of dpp function phenotypes in genetic epistasis tests. Wing specific knockdown of cmi results in incomplete veins towards the distal wing margin that are enhanced by the simultaneous knockdown of dpp. In contrast, the overexpression of a tagged full-length HA-cmi transgene results in ectopic veins that are sensitive to Dpp levels. The knockdown and overexpression of cmi result in reduced and increased Dpp signaling as observed by immunostaining for phospho-MAD (Mother against DPP), a downstream effector of Dpp function. shRNAi depletion of cmi suppresses a tkv reduced function phenotype while the overexpression of HA-cmi enhances tkv RNAi phenotypes. We further show by enhancer reporter assays and chromatin immunoprecipitation that Cmi controls wing vein patterning by regulating dpp transcription directly or indirectly through the 3′ disc regulatory region at the larval stage and through the 5′ shortvein (shv) regulatory region at the pupal stage. Our data reveals that Cmi is a key part of the mechanism that controls wing vein patterning through nuclear receptor regulation of the Dpp signaling pathway.

The homeostasis of Drosophila midgut is maintained by multipotent intestinal stem cells (ISCs), each of which gives rise to a new ISC and an immature daughter cell, enteroblast (EB), after one asymmetric cell division. In Drosophila, the Gal4-UAS system is widely used to manipulate gene expression in a tissue- or cell-specific manner, but in Drosophila midgut, there are no ISC- or EB-specific Gal4 lines available. Here we report the generation and characterization of Dl-Gal4 and Su(H)GBE-Gal4 lines, which are expressed specifically in the ISCs and EBs separately. Additionally, we demonstrate that Dl-Gal4 and Su(H)GBE-Gal4 are expressed in adult midgut progenitors (AMPs) and niche peripheral cells (PCs) separately in larval midgut. These two Gal4 lines will serve as invaluable tools for navigating ISC behaviors.

Adult stem cells maintain tissue homeostasis by continuously replenishing damaged, aged and dead cells in any organism. Five types of region and organ-specific multipotent adult stem cells have been identified in the Drosophila digestive system: intestinal stem cells (ISCs) in the posterior midgut; hindgut intestinal stem cells (HISCs) at the midgut/hindgut junction; renal and nephric stem cells (RNSCs) in the Malpighian Tubules; type I gastric stem cells (GaSCs) at foregut/midgut junction; and type II gastric stem cells (GSSCs) at the middle of the midgut. Despite the fact that each type of stem cell is unique to a particular organ, they share common molecular markers and some regulatory signaling pathways. Due to the simpler tissue structure, ease of performing genetic analysis, and availability of abundant mutants, Drosophila serves as an elegant and powerful model system to study complex stem cell biology. The recent discoveries, particularly in the Drosophila ISC system, have greatly advanced our understanding of stem cell self-renewal, differentiation, and the role of stem cells play in tissue homeostasis/regeneration and adaptive tissue growth.

The spermatogonial stem cells (SSCs) are responsible for the transmission of genetic information from an individual to the next generation. SSCs play critical roles in understanding the basic reproductive biology of gametes and treatments of human infertility. SSCs not only maintain normal spermatogenesis, but also sustain fertility by critically balancing both SSC self-renewal and differentiation. This self-renewal and differentiation in turn is tightly regulated by a combination of intrinsic gene expression within the SSC as well as the extrinsic gene signals from the niche. Increased SSCs self-renewal at the expense of differentiation result in germ cell tumours, on the other hand, higher differentiation at the expense of self-renewal can result in male sterility. Testicular germ cell cancers are the most frequent cancers among young men in industrialized countries. However, understanding the pathogenesis of testis cancer has been difficult because it is formed during foetal development. Recent studies suggest that SSCs can be reprogrammed to become embryonic stem (ES)-like cells to acquire pluripotency. In the present review, we summarize the recent developments in SSCs biology and role of SSC in testicular cancer. We believe that studying the biology of SSCs will not only provide better understanding of stem cell regulation in the testis, but eventually will also be a novel target for male infertility and testicular cancers.