Die Rolle von EZH2 und p57kip2 bezüglich Ausbildung, Reifung und Regeneration peripherer Nerven
Molekulare Biologie und Physiologie von Nerven- und Gliazellen
Zusammenfassung der Projektergebnisse
Peripheral nerve maturation involves strict regulation of myelination onset. Both stimulatory and inhibitory components of peripheral nerve myelination have been described. We found that p57kip2 serves as inhibitor of Schwann cell differentiation which is controlled at transcriptional level by trimethylation of the 5´UTR promotor region by EZH2. Our in vivo data using shRNA based transgenic mice give a hint that permanent downregulation of p57kip2 may induce aberrant peripheral nerve morphologies. However, conditional ablation is necessary to describe the full potential of p57kip2 in the developmental context. Further, we were able to identify PDGF-BB and Nrg1 as promising signalling cues which control p57kip2 activity via Akt phosphorylation.
