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Dissertation/Thesis Abstract

Investigating Developmentally Programmed Germ Cell Remodeling by Endodermal Cell Cannibalism
by Abdu, Yusuff, Ph.D., New York University, 2018, 222; 10682325
Abstract (Summary)

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.

Indexing (document details)
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
Publication Number: 10682325
ISBN: 978-0-355-77366-8
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