Germ stem cell enwrapment by its niche in C. elegans

Abstract

Niches regulate stem cell fate during development and disease. It is thus critical to understand the cellular behaviors that underlie stem cell-niche interactions. Cellular enwrapment of stem cells by their niche is observed in the C. elegans germ stem cell niche, the D. rerio hematopoietic niche, and the D. melanogaster intestinal and lymph niches. This widespread niche behavior is nevertheless difficult to dissect. In the visually and genetically tractable C. elegans germ stem cell niche, the distal tip cell (DTC) functions as a single-cell niche that elaborates to form a plexus of cellular processes enwrapping germ stem cells. Using the DTC niche as a model and tools including live imaging, genetic screens, and tissue-specific knockdown, we elucidate the regulation and function of cellular enwrapping behavior in C. elegans stem cell-niche interactions. In Chapter 2, I identify a set of DTC-autonomous genes including lin-40/MTA1 that directly promote DTC plexus formation. I also identify a set of germline-autonomous genes that indirectly promote enwrapment by the DTC plexus by supporting germ progenitor cell fate, suggesting that germ progenitor cells produce a cue for enwrapment. DTC plexus formation promotes GLP-1/Notch signaling and stem cell fate in enwrapped germ cells, suggesting a positive feedback loop between the niche and stem cells that expands the stem cell pool. In Chapter 3, I show that the adhesion molecules hmr-1/cadherin and sax-7/L1CAM promote DTC plexus formation. Substantiating the idea that germ cells produce a cue for enwrapment, I show that outside the reciprocal interactions within the germ stem cell niche, escaped germ cells induce enwrapment by other somatic tissues. Outside of importance in normal niche establishment, these observations suggest that enwrapment could be coopted in disease states. Chapter 4 discusses the implications of this work.