Primordial germ cells are the founder cells of the gametes. In the mouse, they arise in the posterior region of the gastrula, and migrate through the developing tissues of the embryo to colonize the gonad primordia. Steel factor is a signaling protein required for germ cell survival, and is the ligand for the receptor c-kit, expressed by the migrating germ cells. We have shown recently that Steel factor acts at short range during migration, and also controls germ cell proliferation and motility. This raises the interesting questions of the origins of the Steel factor during migration, and how Steel factor expression is controled. Preliminary data, using a novel reporter mouse that allows visualization of germ cells from the time of their specification in the gastrula, shows that germ cells are surrounded by Steel factor-expressing cells from the time of their formation in the embryo to the time they colonize the gonad primordia. This suggests the presence of a ?traveling niche"""""""" for this important stem cell population during their occupation of different tissues of the embryo. This project aims to test three hypotheses. First, that Steel factor controls germ cell behavior from the time they arise in the embryo. Second, that the short range of Steel factor signaling is due to the expression of membrane-bound Steel factor, that cannot be replaced by the soluble form of Steel factor. Third, the concept of a continuous niche around the germ cells as they migrate requires a mechanism that establishes that niche. We will test the hypothesis that signals from adjacent tissues activate expression of Steel factor in cells immediately around the germ cells at the gastrula stage.
The combination of molecular, cellular and in vivo approaches employed in th is proposal will provide critical new insights into the mechanism how FMRP regulates mRNA translation and local protein synthesis that underlie neuronal network development, and how FMRP deficiency leads to frag ile X mental syndrome, wh ich will also sign ificantly advance our knowledge on trasn lation dependent synaptic palsticity.
| Gu, Ying; Runyan, Christopher; Shoemaker, Amanda et al. (2011) Membrane-bound steel factor maintains a high local concentration for mouse primordial germ cell motility, and defines the region of their migration. PLoS One 6:e25984 |
