Tumor protein Tctp regulates axon development in the embryonic visual system

Abstract

The transcript encoding translationally controlled tumor protein (Tctp), a molecule correlated with aggressive breast cancers, was identified among the most abundant in genome-wide screens of axons, suggesting that Tctp is important in neurons. Here, we tested the role of Tctp in retinal axon development in Xenopus laevis. We report that Tctp deficiency results in stunted and splayed retinotectal projections that fail to innervate the optic tectum at the normal developmental time due to impaired axon extension. Tctp-deficient axons exhibit defects associated with mitochondrial dysfunction and we show that Tctp interacts in the axonal compartment with myeloid cell leukemia 1 (Mcl1), a pro-survival member of the Bcl-2 family. Mcl1 knockdown gives rise to similar axon misprojection phenotypes, and we provide evidence that Tctp's anti-apoptotic activity is necessary for the normal development of the retinotectal projection. The findings suggest that Tctp supports the development of the retinotectal projection via its regulation of pro-survival signalling and axonal mitochondrial homeostasis, and establish a novel and fundamental role for Tctp in vertebrate neural circuitry assembly.