Adenomatous polyposis coli regulates radial axonal sorting and myelination in the PNS

The tumor suppressor protein adenomatous polyposis coli (APC) is multifunctional, participating in the canonical Wnt/β-catenin signal transduction pathway, as well as in modulating cytoskeleton function. Although expressed by Schwann cells, the role that APC plays in these cells and in the myelination of the peripheral nervous system (PNS) is unknown. Therefore, we used the Cre-lox approach to generate a mouse model in which APC expression is specifically eliminated from Schwann cells. These mice display hindlimb weakness and impaired axonal conduction in sciatic nerves. Detailed morphological analyses revealed that APC loss delays radial axonal sorting and PNS myelination. Furthermore, APC loss delays Schwann cell differentiation in vivo, which correlates with persistent activation of the Wnt signaling pathway, and results in perturbed Schwann cell processes extension and lamellipodia formation. In addition, APC deficient Schwann cells display a transient diminution of proliferative capacity. Our data indicate that APC is required by Schwann cells for their timely differentiation to mature, myelinating cells and plays a critical role in radial axonal sorting and PNS myelination.