Investigating the signaling mechanisms required for germ cell differentiation

Brown University, Providence RI

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Abstract

DESCRIPTION (provided by applicant): The proper development of eggs and sperm is required for most animal reproduction. As such, primordial germ cell specification, the setting aside of the cells that give rise to eggs and sperm, is a crucial time in animal development for future reproductive success. In mice and humans, intercellular signals are required to induce germ cell differentiation during development, whereas flies and worms use a distinct, maternally-acquired mechanism to determine their germ cells. The long-term goal of this project is to understand the precise inductive signaling and molecular mechanisms that restrict the germ-cell inducing signals and to determine how these mechanisms contribute to the proper differentiation of the germ cell fate. Nodal signaling is required in both mice and sea stars to se up the developmental axes that restrict the potential to become germ cells. We hypothesize that Nodal signaling restricts the population of cells that can become germ cells. We will rigorously test this hypothesis by perturbing Nodal signaling and determining the precise molecular mechanisms that contribute to the negative accumulation of mRNAs for germ cell specification. In addition, we will define the morphogenetic cellular phenotypes required for the establishment of a germ cell specification niche and determine how Nodal signaling inhibits cells from taking on these morphogenetic cellular traits. These results will be complementary, and integrated into, models of mammalian germ cell induction, but the purpose of this research is to use an organism tractable for cellular and biochemical approaches. Insights into the precise molecular mechanisms that regulate the differentiation of the germ cell fate are crucial to identify novel genes involved in: the genetic basis of infertility, the induction of life-threatening teratomas, ad the proliferative abilities of cancers with upregulated germ-cell associated genes.