Molecular basis of primordial germ cell formation from multipotent stem cells in the polychaete Platynereis dumerilii, an ancestral lophotrochozoan.
Evolution, Anthropology
Final Report Abstract
We obtained the following novel insights into PGC formation in Platynereis: 1. Unlike stated previously, the PGCs form early in development as direct descendants of the mesoblasts. 2. Inhibition of the AKT/GSK3β/β-catenin pathway by a specific AKT inhibitor reduces the number of PGCs, while increasing nuclear β-catenin levels with the GSK3β inhibitor azakenpaullone leads to the formation of supernumerary PGCs. 3. Activation of the AKT/GSK3β/β-catenin pathway by the steroid 17β-estradiol or xenoestrogens (ethinylestradiol, nonylphenol) similary increase PGC numbers. This effect is mediated by the Platynereis estrogen receptor. 4. The responsive phase for the induction of supernumerary PGCs by 17β-estradiol is restricted to 4 – 9 hpf. The ER is down-regulated in larval stages. The active form of RNA polymerase II, indicative of active transcription, is not detectable in larval PGCs. 5. Chromatin remodeling such as a loss in H3K4methylation might constitute a long term silencing mechanism of the PGCs. Perspective: A detailed investigation of the signaling pathways involved in PGC formation and the establishment of transcriptional and mitotic quiescence will constitute the central aspects in the upcoming renewal application.
