Environmental cues regulating primordial germ cell development

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DESCRIPTION (provided by applicant): Pluripotent stem cells can divide and differentiate to give rise to multiple cell types. These cells have enormous therapeutic potential for replacing tissue loss caused by disease or injury. To harness this potential, it is vital to understand the signaling interactions that control stem cell behavior in vivo. PGCs are the pluripotent cell population that will give rise to the gametes. Using a line of mice expressing the live cell marker GFP under control of a germ cell specific promoter, it is now possible to directly observe the behavior of living primordial germ cells as they migrate towards and colonize the embryonic gonads. This assay provides a novel opportunity to test how PGCs interact with their environment. Data from this assay has demonstrated that the bone morphogenetic family plays a pivotal role in PGC migration. Also, preliminary data indicates that BMPs regulate expression of a network of genes within the soma and within PGCs that control PGC numbers, motility, and ability to differentiate. This study will test the role of BMP signaling in PGC migration using temporal and tissue specific gene targeting in the mouse (Aim 1). BMP-responsive regulatory elements will be identified in the Kitl gene (Aim 2). Finally, cell transplantation assays and ablation experiments will be used to examine how different environments affect PGC behavior (Aims 3 and 4). Our ultimate goal is to understand the cellular and molecular interactions that control PGC migration and differentiation. This study will provide insight into how stem cell development is coordinated. Additionally, errors in PGC migration contribute to human infertility and germ cell tumors. Data from this study will shed light on these processes.