Daam2-PIP5K is a regulatory pathway for Wnt signaling and therapeutic target for remyelination in the CNS.

ABSTRACT: Wnt signaling plays an essential role in developmental and regenerative myelination of the CNS; however, contributions of proximal regulators of the Wnt receptor complex to these processes remain undefined. To identify components of the Wnt pathway that regulate these processes, we applied a multifaceted discovery platform and found that Daam2-PIP5K comprise a novel pathway regulating Wnt signaling and myelination. Using dorsal patterning of the chick spinal cord we found that Daam2 promotes Wnt signaling and receptor complex formation through PIP5K-PIP2. Analysis of Daam2 function in oligodendrocytes (OLs) revealed that it suppresses OL differentiation during development, after white matter injury (WMI), and is expressed in human white matter lesions. These findings suggest a pharmacologi

SUBMITTER: Lee HK 

PROVIDER: S-EPMC4402944 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature