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Curr Biol. 2019 Mar 4;29(5):823-833.e5. doi: 10.1016/j.cub.2019.01.056. Epub 2019 Feb 21.

Ectopic Germ Cells Can Induce Niche-like Enwrapment by Neighboring Body Wall Muscle.

Author information

1
Department of Biology, Duke University, Durham, NC 27708, USA.
2
Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
3
Skirball Institute of Biomolecular Medicine, Departments of Cell Biology and Pathology, New York University School of Medicine, New York, NY 10016, USA.
4
Department of Biology, Duke University, Durham, NC 27708, USA; Regeneration Next, Duke University, Durham, NC 27708, USA. Electronic address: david.sherwood@duke.edu.

Abstract

Niche cell enwrapment of stem cells and their differentiating progeny is common and provides a specialized signaling and protective environment. Elucidating the mechanisms underlying enwrapment behavior has important basic and clinical significance in not only understanding how niches are formed and maintained but also how they can be engineered and how they are misregulated in human pathologies, such as cancer. Previous work in C. elegans found that, when germ cells, which are enwrapped by somatic gonadal niche cells, are freed into the body cavity, they embed into other tissues. We investigated this phenomenon using live-cell imaging and discovered that ectopic germ cells preferentially induce body-wall muscle to extend cellular processes that enwrap the germ cells, the extent of which was strikingly similar to the distal tip cell (DTC)-germ stem cell niche. Enwrapment was specific for escaped germ cells, and genetic analysis revealed it did not depend on pathways that control cell death and engulfment or muscle arm extension. Instead, using a large-scale RNAi screen and GFP knockin strains, we discovered that the enwrapping behavior of muscle relied upon the same suite of cell-cell adhesion molecules that functioned in the endogenous niche: the C. elegans E-cadherin HMR-1, its intracellular associates α-catenin (HMP-1) and β-catenin (HMP-2), and the L1CAM protein SAX-7. This ectopic niche-like behavior resembles the seed-and-soil model of cancer metastasis and offers a new model to understand factors regulating ectopic niche formation.

KEYWORDS:

C. elegans; E-cadherin; L1CAM; cellular enwrapment; distal tip cell (DTC); ectopic niche; germ cell; stem cell; stem cell niche

PMID:
30799241
PMCID:
PMC6457669
[Available on 2020-03-04]
DOI:
10.1016/j.cub.2019.01.056

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