Article

Developmentally programmed germ cell remodelling by endodermal cell cannibalism

  • Nature Cell Biology volume 18, pages 13021310 (2016)
  • doi:10.1038/ncb3439
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Abstract

Primordial germ cells (PGCs) in many species associate intimately with endodermal cells, but the significance of such interactions is largely unexplored. Here, we show that Caenorhabditis elegans PGCs form lobes that are removed and digested by endodermal cells, dramatically altering PGC size and mitochondrial content. We demonstrate that endodermal cells do not scavenge lobes PGCs shed, but rather, actively remove lobes from the cell body. CED-10 (Rac)-induced actin, DYN-1 (dynamin) and LST-4 (SNX9) transiently surround lobe necks and are required within endodermal cells for lobe scission, suggesting that scission occurs through a mechanism resembling vesicle endocytosis. These findings reveal an unexpected role for endoderm in altering the contents of embryonic PGCs, and define a form of developmentally programmed cell remodelling involving intercellular cannibalism. Active roles for engulfing cells have been proposed in several neuronal remodelling events, suggesting that intercellular cannibalism may be a more widespread method used to shape cells than previously thought.

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Acknowledgements

We thank the Caenorhabditis Genetics Center (CGC), National Bioresource Project (NBRP), and Z. Zhou (Baylor College of Medicine, USA) for providing worm strains. Caged rhodamine dextran was a gift from K. Oegema (University of California, San Diego). We thank T. Hurd (NYU School of Medicine, USA) for sharing TMRE dye and mitochondrial discussion; J. H. Choi (NYU School of Medicine, USA) for assistance in developing the technique for cell culture experiments; D. McIntyre (NYU School of Medicine, USA) for designing a nitrogen gas immobilization chamber for embryos; and L. Christiaen (New York University, USA), N. Ringstad (NYU School of Medicine, USA), T. Hurd (NYU School of Medicine, USA) and members of the Nance laboratory for comments on the manuscript. Library preparation and sequencing of genomic DNA samples was performed at the NYULMC Genome Technology Center, which is partially supported by a Cancer Center Support Grant (P30CA016087) at the Laura and Isaac Perlmutter Cancer Center. Funding was provided by the NIH (R35GM118081, R21HD084809 to J.N.), NYSTEM (C029561 to J.N.) and HHMI (J.M.H., T.-L.C). Y.A. is an HHMI International Student Research fellow.

Author information

Affiliations

  1. Helen L. and Martin S. Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, NYU School of Medicine, New York, New York 10016, USA

    • Yusuff Abdu
    • , Chelsea Maniscalco
    •  & Jeremy Nance
  2. Advanced Imaging Center, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia 20147, USA

    • John M. Heddleston
    •  & Teng-Leong Chew
  3. Department of Cell Biology, NYU School of Medicine, New York, New York 10016, USA

    • Jeremy Nance

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Contributions

Y.A. and J.N. designed experiments. C.M. performed and analysed cell culture, MOMA-1 imaging, and end-1 end-3 embryo experiments. Y.A. performed and analysed all other experiments, and J.H. and T.-L.C. assisted with experiments on the lattice light-sheet microscope. Y.A. and J.N. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Jeremy Nance.

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Videos

  1. 1.

    PGC lobe formation.

    Embryo is oriented posterior to the left, and turns from a ventral view to a lateral view (dorsal up) as the movie progresses. PGC and endodermal cell membranes are labeled. PGC lobes (‘L’) begin forming 50 min into the movie and embed into endodermal cells.

  2. 2.

    Rendering of PGC lobes embedded into endodermal cells.

    Rendered data from a 2-fold embryo expressing endoderm and PGC surface markers. PGCs (magenta) extend lobes into adjacent endodermal cells (green).

  3. 3.

    Lobe formation in a cultured PGC.

    PGC membranes and nucleus are labeled. The nucleus moves to one side of the cell and lobe (‘L’) extends from the opposite side beginning at 150 min into the movie.

  4. 4.

    P granule movement into PGC lobes.

    Embryo is oriented posterior to the left. Before lobe formation, all P granules (PGL-1-RFP) are found at the nuclear periphery. A P granule can be seen detaching from the nuclear periphery and moving into the lobe (‘L’) beginning at 42 min into the movie.

  5. 5.

    Mitochondria in PGC lobes.

    Embryo is oriented posterior to the left. All cell membranes are labeled with GFP (PGC membranes are brighter), and mitochondria within PGCs are labeled with mCh-MOMA-1 (green and red channels were switched). Both PGCs are initially visible, then one moves out of the focal plane. Lobe formation begins 16 min into the movie, and mitochondria can be seen localizing preferentially to the lobe (‘L’).