Tumor protein Tctp regulates axon development in the embryonic visual system
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Updated: Mar 25, 2026
Whole-mount Imaging of Mouse Embryo Sensory Axon Projections
Published on: December 9, 2014
Cláudio Gouveia Roque1, Hovy Ho-Wai Wong2, Julie Qiaojin Lin2
1Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK Doctoral Programme in Experimental Biology and Biomedicine, Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra 3004-517, Portugal.
Abstract:
The transcript encoding translationally controlled tumor protein (Tctp), a molecule associated 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 owing 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 Bcl2 family. Mcl1 knockdown gives rise to similar axon misprojection phenotypes, and we provide evidence that the anti-apoptotic activity of Tctp is necessary for the normal development of the retinotectal projection. These 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.
Insights
Translationally controlled tumor protein (Tctp) is crucial for retinal axon development in Xenopus. Tctp deficiency impairs axon extension and neural circuitry assembly by affecting mitochondrial function and survival signaling.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- Translationally controlled tumor protein (Tctp) is linked to aggressive breast cancers.
- Genome-wide screens identified Tctp transcripts as abundant in axons, suggesting a neuronal role.
Purpose of the Study:
- To investigate the role of Tctp in retinal axon development in Xenopus laevis.
- To elucidate the molecular mechanisms underlying Tctp's function in neural circuitry assembly.
Main Methods:
- Tctp deficiency was induced in Xenopus laevis.
- Retinotectal projections were analyzed for axon extension and innervation.
- Axonal mitochondrial function and interactions with Mcl1 were assessed.
- Mcl1 knockdown was performed to compare phenotypes.
Main Results:
- Tctp deficiency led to stunted and splayed retinotectal projections with impaired axon extension.
- Axons lacking Tctp showed mitochondrial dysfunction.
- Tctp interacts with the pro-survival protein Mcl1 in the axonal compartment.
- Mcl1 knockdown phenocopied Tctp deficiency, and Tctp's anti-apoptotic activity was essential.
Conclusions:
- Tctp is essential for normal retinotectal projection development in Xenopus.
- Tctp supports axon extension and innervation by regulating pro-survival signaling and axonal mitochondrial homeostasis.
- Tctp plays a fundamental role in vertebrate neural circuitry assembly.
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