View Program - 63rd Annual Drosophila Research Conference

Niches have been well-established as a source for important extrinsic components that regulate the balance between progenitor cell maintenance and differentiation in tissues. Most well-studied niches are positioned reproducibly within tissues, and are comprised of an organized collective of cells. This implies that formation of niche structure is regulated, and suggests that the tissue-specific structure of niches is pertinent to the underlying biology of the tissue that the niche supports. However, mechanisms that determine the initial organization of cells constituting a niche, and the location of the niche within a tissue remain less-understood. To investigate mechanisms of niche formation, we use the posterior signaling center (PSC)—the niche of the larval lymph gland—as a model niche. The PSC niche maintains stem cell-like hematopoietic progenitors that eventually differentiate into mature hemocytes that respond to immune challenges and infliction of wounds, and replenish hemolymph during homeostasis. Initial formation of the PSC occurs during embryogenesis: PSC cells are specified laterally during mid-embryogenesis, and in late embryos, the PSC resides at the dorsal surface of the embryo, coalesced at the posterior of the lymph gland. Preliminary live-imaging of PSC formation revealed that alary muscle (AM) and visceral mesoderm (vm), two tissues nearby the PSC, move towards the dorsal midline in concordance with the PSC. Thus, we hypothesized that one of these tissues, AM or vm, sends guidance cues that direct PSC migration towards the dorsal midline/lymph gland posterior. Using tissue-specific ablation of the AM, we demonstrate that it is not required for PSC formation. However, analysis of late-stage mutants that lack visceral mesoderm shows that fewer PSC cells are present at the lymph gland posterior, suggesting a requirement for vm in the formation of the PSC. Future experiments will investigate if, in the absence of vm, fewer PSC cells were specified, or some PSC cells underwent apoptosis, or PSC cells were misplaced within the embryo during migration – the latter of which would suggest that vm sends a directional or competency cue important for PSC cell migration.

Uncovering the mechanism of hematopoietic niche formation