Environmental and developmental regulation of primordial germ cell proliferation in the c. Elegans larval gonad

Active Project Grant Awarded Last action

Award ID
F32HD123658
Recipient
Awarding agency
Obligated
$79,000

Award facts

Assistance listing
93.865 Child Health and Human Development Extramural Research
Completion date 0% complete
Place of performance
Madison, WI 53715, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Germ cells are essential to sustain life in sexually reproducing organisms. Primordial germ cells (pgcs) are a population of germline stem cells specified during embryonic development. PGC division is dictated by signaling from the localized microenvironment called the niche. Understanding how the niche relays environmental and developmental cues to instruct cell division is critical to maintain healthy germ cells. Using c. Elegans, i will investigate the signals required to regulate PGC division. The c. Elegans larval gonad is comprised of two pgcs, two somatic gonadal precursors (sgps) and a thin, specialized extracellular matrix called the basement membrane (BM) surrounding the four cells. Pgcs are quiescent, but upon embryo hatching and feeding, pgcs exit quiescence and divide to form the germline stem cells (gscs) in the first larval stage (L1). While IT's known the notch signaling pathway is essential to maintain the adult gscs, the signals required to initiate PGC division are unknown. PGC quiescence is regulated by two inputs: the tumor- suppressor gene pten/DAF-18 and the BM. In DAF-18 mutants, pgcs precociously divide in the absence of food, suggesting a pro-mitotic environmental signal from nutritional inputs regulates PGC division. Genetic depletion of the gonadal BM induces notch signaling in pgcs, resulting in their precocious division. IT's unclear how the BM-mediated brake on PGC quiescence is relieved as the gonad proliferates. PGC proliferation could be induced from compositional changes within the BM or signaling changes between the BM and the sgps or pgcs. I propose to investigate the role of notch signaling, firstly whether IT's required for PGC divisions and secondly whether the precocious division in DAF-18 mutants is notch-dependent. I will also investigate the how the BM mediates PGC proliferation, either through changes in its composition or changes in BM-mediated growth factor signaling. Using a combination of genetic and quantitative imaging tools, i hope to understand how the niche uses highly conserved inputs (notch, pten, BM) to regulate germ cell division and healthy germ cells.

Quick answers

Who received award F32HD123658?

F32HD123658 was awarded to University Of Wisconsin System by National Institute of Child Health and Human Development (National Institutes of Health) on February 1, 2027.

How much is award F32HD123658 worth?

$79,000 has been obligated on F32HD123658.

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