Nrg1 and ErbB receptors in Schwann cell development and myelination

Project Leaders: Alistair Garratt e-mail/Carmen Birchmeier e-mail

 

The Nrg1 gene encodes factors of the EGF family that signal via ErbB2/3 receptor tyrosine kinases. Nrg1 provides key axonal signals that control Schwann cell development and myelination. In normal development, myelin growth ceases around 2-3 weeks of postnatal life. During the second funding period of the SFB, we found that sustained activation of the MAP kinase pathway results in continuous myelin growth. We also investigated the role of Nrg1, ErbB3 and Shp2 signaling and showed that these provide essential cues for Schwann cell development and myelination. Unexpectedly, we found that the activation of the Map kinase pathway in Schwann cells suffices to substitute for the absence of Nrg1/ErbB3 signals. In particular, activation of the MAP kinase pathway rescued transcriptional and translational responses caused by attenuation of Nrg1/ErbB signaling. Further, we characterized the role of c-Maf in myelination. We aim to define in the future the role of MAP kinase signaling in the control of lipid biosynthesis, an important aspect of the myelination program, and assess whether activation of this pathway suffices to re-initiate myelination once it has ceased. Further, the mechanism by which Nrg1/ErbB signaling controls c-Maf function during myelination will be analyzed. In addition, we aim to study the role of two new proteins that might be important in Schwann cell biology, Par3 and Megf10.