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

Benayahu Elbaz, Maria Traka, Rejani B. Kunjamma, Danuta Dukala, Amanda Brosius Lutz, E. S. Anton, Ben A. Barres, Betty Soliven, Brian Popko*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The tumor suppressor protein adenomatous polyposis coli (APC) is multifunctional – it participates in the canonical Wnt/β-catenin signal transduction pathway as well as modulating cytoskeleton function. Although APC is expressed by Schwann cells, the role that it 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 extension of Schwann cell processes and disrupted 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 crucial role in radial axonal sorting and PNS myelination.

Original languageEnglish (US)
Pages (from-to)2356-2366
Number of pages11
JournalDevelopment (Cambridge)
Volume143
Issue number13
DOIs
StatePublished - Jul 1 2016

Keywords

  • Adenomatous polyposis coli
  • PNS
  • Radial axonal sorting
  • Schwann cells
  • Wnt signalling

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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