Primordial germ cells (PGCs) are the precursors of the gametes. Defective PGC development results in reduction or elimination of germ cells and ultimately causes infertility in humans, which affects 10?15% of couples. During development, PGCs are born much earlier than the formation of the gonads. PGCs must manage to survive in the non-protective somatic environment for a long time and later migrate long distances to find the gonads. Specification of PGCs and their proliferation during early stages are crucial to ensure that sufficient number of PGCs can reach the gonads and differentiate into gametes. A large body of literature has demonstrated that before migrating into the gonads, PGC development relies heavily on translational and post-translational regulatory mechanisms. Understanding how PGC development is operated at the translational and post-translation levels thus is highly relevant to human reproductive health. My laboratory studies early PGC development using Xenopus as a model. We recently reported that maternal Dead End1 (Dnd1) is important for asymmetric localization of mRNA in the oocyte. After fertilization, Dnd1 recruits the translational machinery to nanos mRNA and promotes nanos translation. Through this mechanism, Dnd1 prevents somatic differentiation of PGCs and protects their totipotency. Our recent preliminary results reveal that Dnd1 is rapidly degraded in the oocyte by the ubiquitin- independent proteasome system. In order for Dnd1 to accumulate and promote nanos translation after fertilization, RNAs coding for proteasome activators must be separated from dnd1 and other germline specific maternal factors during the oocyte-to-embryo transition. We propose to study how this novel mRNA translocation event prepares for the initiation of PGC development after fertilization and investigate how RNAs coding for proteasome activators are separated from dnd1 and other germline specific maternal factors during the oocyte-to-embryo transition. Moreover, we have made an exciting finding that the first wave of PGC proliferation is regulated by maternal Dzip1. We will determine if Dzip1 regulates PGC proliferation via binding and modifying the activities of germline specific RNA-binding proteins. Furthermore, we will identify the zygotic transcriptional network that acts downstream of Dzip1 to control PGC proliferation. These works will make important contributions to our understanding of basic cell, reproductive, and developmental biology.
Since human infertility affects 10?15% of couples, a better understanding of the development of primordial germ cells (PGCs), which give rise to sperms and eggs, is highly relevant to human reproductive health. We study how PGC development is initiated and how PGCs proliferate during early stages. Findings from our research will advance the knowledge on stem cell, developmental, and reproductive biology.
