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A4: From neural stem cell to regenerated spinal cord: Cell proliferation and diversification of neural stem cells during spinal cord regeneration in Ambystoma mexicanium

Project leader: Prof. Dr. E. M. Tanaka

In the last funding period we initiated analysis of the WNT5 pathway as an injury induced regulator for axolotl spinal cord regeneration. We demonstrated the role of PCP signalling in spinal cord regeneration via over-expression of core planar cell polarity (PCP) components, Prickle1 and Vang-like2.  We showed that planar cell polarity controls processes including oriented cell divisions during spinal cord regeneration that facilitates the initial outgrowth of the spinal cord tube.

Our most recent results also implicate WNT signalling in the decision to remain epithelial or to become mesenchymal in the spinal cord.  Over-expression of a dominant negative dishhevelled mutant results in the whole spinal cord converting to a mesenchymal phenotype.

Here we will molecularly dissect which downstream WNT pathways govern whether a stem cell remains epithelial and self-renewing or becomes mesenchymal and non-self-renewing.  We will investigate whether this pathway relies on non-canonical or canonical WNT signalling.  Furthermore, we will investigate the contribution of parallel TGFb and FGF signalling in this process.  We will also test whether differences in WNT5 mediated non-canonical signalling contribute to this difference in regeneration potential between axolotl and zebrafish.


« October 2019 »

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