Distant activation of Notch signaling induces stem cell niche assembly

PLoS Genet. 2021 Mar 29;17(3):e1009489. doi: 10.1371/journal.pgen.1009489. eCollection 2021 Mar.

Abstract

Here we show that multiple modes of Notch signaling activation specify the complexity of spatial cellular interactions necessary for stem cell niche assembly. In particular, we studied the formation of the germline stem cell niche in Drosophila ovaries, which is a two-step process whereby terminal filaments are formed first. Then, terminal filaments signal to the adjacent cap cell precursors, resulting in Notch signaling activation, which is necessary for the lifelong acquisition of stem cell niche cell fate. The genetic data suggest that in order to initiate the process of stem cell niche assembly, Notch signaling is activated among non-equipotent cells via distant induction, where germline Delta is delivered to somatic cells located several diameters away via cellular projections generated by primordial germ cells. At the same time, to ensure the robustness of niche formation, terminal filament cell fate can also be induced by somatic Delta via cis- or trans-inhibition. This exemplifies a double security mechanism that guarantees that the germline stem cell niche is formed, since it is indispensable for the adjacent germline precursor cells to acquire and maintain stemness necessary for successful reproduction. These findings contribute to our understanding of the formation of stem cell niches in their natural environment, which is important for stem cell biology and regenerative medicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Drosophila
  • Female
  • Germ Cells / metabolism
  • Models, Biological
  • Mutation
  • Organogenesis / genetics
  • Ovary / embryology
  • Ovary / metabolism
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*
  • Signal Transduction*
  • Stem Cell Niche* / genetics
  • Stem Cells / metabolism*

Substances

  • Receptors, Notch

Grants and funding

This work was supported by the EMBO YIP Program, Max Planck Society, and Hannover Medical School. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.