Abstract
BackgroundThe directional migration and the following development of primordial germ cells (PGCs) during gonad formation are key steps for germline development. It has been proposed that the interaction between germ cells and genital ridge (GR) somatic cells plays essential roles in this process. However, the in vivo functional requirements of GR somatic cells in germ cell development are largely unknown.ResultsWt1 mutation (Wt1R394W/R394W) results in GR agenesis through mitotic arrest of coelomic epitheliums. In this study, we employed the GR-deficient mouse model, Wt1R394W/R394W, to investigate the roles of GR somatic cells in PGC migration and proliferation. We found that the number of PGCs was dramatically reduced in GR-deficient embryos at embryonic day (E) 11.5 and E12.5 due to decreased proliferation of PGCs, involving low levels of BMP signaling. In contrast, the germ cells in Wt1R394W/R394W embryos were still mitotically active at E13.5, while all the germ cells in control embryos underwent mitotic arrest at this stage. Strikingly, the directional migration of PGCs was not affected by the absence of GR somatic cells. Most of the PGCs reached the mesenchyme under the coelomic epithelium at E10.5 and no ectopic PGCs were noted in GR-deficient embryos. However, the precise positioning of PGCs was disrupted.ConclusionsOur work provides in vivo evidence that the proliferation of germ cells is precisely regulated by GR somatic cells during different stages of gonad development. GR somatic cells are probably dispensable for the directional migration of PGCs, but they are required for precise positioning of PGCs at the final step of migration.
Highlights
The directional migration and the following development of primordial germ cells (PGCs) during gonad formation are key steps for germline development
Abnormal proliferation of PGCs was observed in Wt1R394W/R394W embryos at E13.5. These results suggest that the proliferation of germ cells during the early stage of gonad development is precisely regulated by genital ridge (GR) somatic cells, and the GR somatic cells are probably dispensable for directional migration of PGCs
The results of the terminal deoxynucleotidyl transferasemediated deoxyuridine triphosphate nick endlabeling (TUNEL) assay showed that the number of apoptotic cells was not increased in Wilms’ tumor 1 (WT1)-positive coelomic epitheliums of Wt1R394W/R394W embryos compared to control embryos (Figure 2A, C), which was inconsistent with the previous study [33]
Summary
The directional migration and the following development of primordial germ cells (PGCs) during gonad formation are key steps for germline development. PGCs must become motile and actively migrate across the embryo to reach the developing genital ridge (GR) and form the functional gonads in combination with surrounding somatic cells [3]. Stromal cell-derived factor 1 (Sdf1) is the most promising attractant signaling candidate, which is primarily expressed in the GR and surrounding mesenchyme; its receptor, Cxcr, is expressed in PGCs [9,10,11]. The importance of this chemokine signaling for PGCs migration and colonization has been demonstrated by studying gene knockout mouse models [9,11]. The precise function of GR somatic cells in PGCs migration remains to be elucidated
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