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

48 Pages Posted: 4 Dec 2018 Sneak Peek Status: Under Review

See all articles by Kacy L. Gordon

Kacy L. Gordon

Duke University - Department of Biology

Sara G. Payne

Duke University - Department of Biology

Lara M. Linden-High

Duke University - Department of Biology

Ariel M. Pani

University of North Carolina (UNC) at Chapel Hill - Department of Biology

Bob Goldstein

University of North Carolina (UNC) at Chapel Hill - Department of Biology

E. Jane Albert Hubbard

New York University (NYU) - Skirball Institute of Biomolecular Medicine

David R. Sherwood

Duke University - Department of Biology

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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 ectopic 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 knock-in 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 a-catenin (HMP-1) and β-catenin (HMP-2A), 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: cellular enwrapment, ectopic niche, stem cell, germ cell, E-cadherin, L1CAM, C. elegans

Suggested Citation

Gordon, Kacy L. and Payne, Sara G. and Linden-High, Lara M. and Pani, Ariel M. and Goldstein, Bob and Hubbard, E. Jane Albert and Sherwood, David R., Ectopic Germ Cells Can Induce Niche-Like Enwrapment by Neighboring Body Wall Muscle (December 4, 2018). Available at SSRN: https://ssrn.com/abstract=3295646 or http://dx.doi.org/10.2139/ssrn.3295646
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Kacy L. Gordon (Contact Author)

Duke University - Department of Biology

Durham, NC 27708
United States

Sara G. Payne

Duke University - Department of Biology

Durham, NC 27708
United States

Lara M. Linden-High

Duke University - Department of Biology

Durham, NC 27708
United States

Ariel M. Pani

University of North Carolina (UNC) at Chapel Hill - Department of Biology

Coker Hall, CB #3280
120 South Road
Chapel Hill, NC
United States

Bob Goldstein

University of North Carolina (UNC) at Chapel Hill - Department of Biology

Coker Hall, CB #3280
120 South Road
Chapel Hill, NC
United States

E. Jane Albert Hubbard

New York University (NYU) - Skirball Institute of Biomolecular Medicine

540 First Avenue
New York, NY 10016
United States

David R. Sherwood

Duke University - Department of Biology ( email )

Durham, NC 27708
United States