During development, primordial germ cells (PGCs) form early and undergo several specialized molecular and cellular remodeling events to establish and maintain the germ cell program. A conserved behavior of PGCs is to intimately associate with endodermal cells. Yet, the significance of this germ cell-endoderm association remains largely unexplored. Midway through the embryogenesis of Caenorhabditis elegans, PGCs form large protrusions called lobes that become embedded inside the adjacent endodermal cells. The fate of the lobes and the significance PGC-endoderm interaction has remained a mystery. Here, using live fluorescent imaging, we show that PGC lobes are actively removed and degraded by endodermal cells, dramatically reducing PGC size and mitochondrial content. We demonstrate that endodermal cells do not scavenge lobes PGCs shed, but rather, actively cannibalize lobes from the PGC cell body through a developmentally regulated mechanism. Also, we find that endodermal CED-10/Rac1-induced actin, DYN-1/dynamin, and LST-4/SNX9 transiently surround lobe necks and are required for lobe scission. Our results suggest that scission occurs through a mechanism resembling mitochondrial fission in animal cells where a constriction machinery in the outer membrane promotes scission in both outer and inner membranes. Interestingly, we find that PGC mitochondria are enriched in potentially damaging reactive oxygen species (ROS) prior to their elimination. We hypothesize that lobe cannibalism protects PGCs by reducing mitochondrial-produced ROS within PGCs. These findings reveal an unexpected role for endoderm in altering the contents of embryonic PGCs, and define a form of developmentally programmed cell remodeling involving intercellular cannibalism. Active roles for engulfing cells have been proposed in several neuronal remodeling events, suggesting that intercellular cannibalism may be a more widespread method used to shape cells.
|Advisor:||Nance, Jeremy F.|
|Commitee:||Christiaen, Lionel, Lehmann, Ruth, Ringstad, Niels|
|School:||New York University|
|Department:||Basic Medical Science|
|School Location:||United States -- New York|
|Source:||DAI-B 79/08(E), Dissertation Abstracts International|
|Subjects:||Genetics, Cellular biology, Developmental biology|
|Keywords:||Cell cannibalism, Cell remodeling, Germ cells, Mitochondria|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be