Our long-term goal is to understand the developmental and molecular basis for soma-germline interactions that influence germline proliferation and differentiation. The germ cells of most animals, including mammals, proliferate extensively during development. This proliferation is required to produce an adequate progenitor pool for adult gamete production. We are investigating how somatic signals control germline proliferation, including the role of nutrition-sensitive signaling pathways in this control. These mechanisms are not well understood and can be studied best in a whole-organism context that is amenable to genetic and molecular analysis, such as the nematode C. elegans. Despite the evolutionary distance between C. elegans and mammals, molecular pathways are largely conserved. Therefore, these studies will likely provide broadly applicable results and lend insights into general aspects of cell proliferation control in humans with implications for fertility, cancer, and stem cell biology. Recent studies from our lab implicate the distal sheath cells and the insulin-like pathway in the control of germline proliferation in C. elegans. Using molecular-genetic and biochemical techniques, as well as anatomical manipulations, we propose to identify and chacterize the relevant targets of the pathway for germline proliferation, to elucidate the role of the S6 kinase in this context, and to investigate the molecular basis for the influence of nutrition on germline proliferation.

Public Health Relevance

Germ cells are the link from generation to generation and must proliferate to ensure fertility, and germ cell proliferation is controlled by interaction with neighboring cells and by hormones and nutrition. We study conserved molecular pathways that control germ cell proliferation. These investigations inform similar processes in humans with implications for fertility, cancer, and stem cell biology.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM061706-13
Application #
8449168
Study Section
Cellular, Molecular and Integrative Reproduction Study Section (CMIR)
Program Officer
Gaillard, Shawn R
Project Start
2000-07-01
Project End
2014-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
13
Fiscal Year
2013
Total Cost
$348,742
Indirect Cost
$142,386
Name
New York University
Department
Pathology
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Roy, Debasmita; Michaelson, David; Hochman, Tsivia et al. (2016) Cell cycle features of C. elegans germline stem/progenitor cells vary temporally and spatially. Dev Biol 409:261-71
Qin, Zhao; Hubbard, E Jane Albert (2015) Non-autonomous DAF-16/FOXO activity antagonizes age-related loss of C. elegans germline stem/progenitor cells. Nat Commun 6:7107
Atwell, Kathryn; Qin, Zhao; Gavaghan, David et al. (2015) Mechano-logical model of C. elegans germ line suggests feedback on the cell cycle. Development 142:3902-11
Deng, Xinzhu; Michaelson, David; Tchieu, Jason et al. (2015) Targeting Homologous Recombination in Notch-Driven C. elegans Stem Cell and Human Tumors. PLoS One 10:e0127862
Hubbard, E Jane Albert (2014) FLP/FRT and Cre/lox recombination technology in C. elegans. Methods 68:417-24
Hubbard, E Jane Albert; Korta, Dorota Z; Dalfó, Diana (2013) Physiological control of germline development. Adv Exp Med Biol 757:101-31
Korta, Dorota Z; Tuck, Simon; Hubbard, E Jane Albert (2012) S6K links cell fate, cell cycle and nutrient response in C. elegans germline stem/progenitor cells. Development 139:859-70
Dalfó, Diana; Michaelson, David; Hubbard, E Jane Albert (2012) Sensory regulation of the C. elegans germline through TGF-β-dependent signaling in the niche. Curr Biol 22:712-9
Setty, Yaki; Dalfó, Diana; Korta, Dorota Z et al. (2012) A model of stem cell population dynamics: in silico analysis and in vivo validation. Development 139:47-56
Hubbard, E Jane Albert (2011) Insulin and germline proliferation in Caenorhabditis elegans. Vitam Horm 87:61-77

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