Eater cooperates with Multiplexin to drive the formation of hematopoietic compartments

Elife. 2020 Oct 7:9:e57297. doi: 10.7554/eLife.57297.

Abstract

Blood development in multicellular organisms relies on specific tissue microenvironments that nurture hematopoietic precursors and promote their self-renewal, proliferation, and differentiation. The mechanisms driving blood cell homing and their interactions with hematopoietic microenvironments remain poorly understood. Here, we use the Drosophila melanogaster model to reveal a pivotal role for basement membrane composition in the formation of hematopoietic compartments. We demonstrate that by modulating extracellular matrix components, the fly blood cells known as hemocytes can be relocated to tissue surfaces where they function similarly to their natural hematopoietic environment. We establish that the Collagen XV/XVIII ortholog Multiplexin in the tissue-basement membranes and the phagocytosis receptor Eater on the hemocytes physically interact and are necessary and sufficient to induce immune cell-tissue association. These results highlight the cooperation of Multiplexin and Eater as an integral part of a homing mechanism that specifies and maintains hematopoietic sites in Drosophila.

Keywords: D. melanogaster; ECM; cell-matrix interaction; developmental biology; eater; hematopoietic microenvironment; immune cell homing; immunology; inflammation; multiplexin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basement Membrane / metabolism
  • Cell Differentiation
  • Chondroitin Sulfate Proteoglycans / genetics*
  • Chondroitin Sulfate Proteoglycans / metabolism
  • Collagen / genetics*
  • Collagen / metabolism
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / physiology*
  • Hematopoiesis / genetics*
  • Hematopoietic System / metabolism*
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism

Substances

  • Chondroitin Sulfate Proteoglycans
  • Drosophila Proteins
  • Mp protein, Drosophila
  • Receptors, Cell Surface
  • eater protein, Drosophila
  • Collagen