Primordial germ cells (PGCs) are embryonic precursors of the adult germ line. At early stages of embryogenesis, PGCs segregate from somatic cells and exhibit distinctive behaviors and regulation. One conserved PGC behavior, which occurs in both invertebrates and vertebrates, is physical association with endodermal cells. The significance of PGC-endoderm interactions is not known. By performing live fluorescent imaging of PGCs and endoderm in the anatomically simple C. elegans embryo, we have discovered an unexpected and novel role for endoderm in remodeling PGC contents. Specifically, we observe that PGCs extend large cytoplasmic lobes, which are actively bitten off and digested by endodermal cells. Endoderm-assisted remodeling allows PGCs to discard cellular components, such as the majority of their mitochondria, and we hypothesize that remodeling prepares PGCs for their impending transition to adult germ cells. The broad goal of this exploratory proposal is to establish the C. elegans embryo as a model to investigate the purpose and mechanism of endoderm-PGC interactions. Our specific goals are to (1) to test the hypothesis that a subset of cell corpse engulfment genes promotes endoderm-assisted PGC remodeling; and (2) to clone and characterize existing mutants, and to identify new mutants, which fail in PGC remodeling. These studies will provide a basis for establishing whether endoderm-assisted PGC remodeling is important for adult germ cell function in C. elegans and other species. In addition, our findings may yield new insights into conceptually analogous remodeling events, such as the shedding of photoreceptor outer segments and the remodeling of neurons.
For reasons that are not known, primordial germ cells (the cells that give rise to sperm and eggs) associate during embryogenesis with endoderm (the cells that give rise to the digestive tract). Using the nematode C. elegans as a model, we have discovered that endodermal cells bite off and digest large portions of primordial germ cells to remodel their contents. We speculate that primordial germ cell remodeling is important for their function, and thus for fertility, and propose experiments to determine how and why this event occurs.
| Abdu, Yusuff; Maniscalco, Chelsea; Heddleston, John M et al. (2016) Developmentally programmed germ cell remodelling by endodermal cell cannibalism. Nat Cell Biol 18:1302-1310 |
