title: Tumor protein Tctp regulates axon development in the embryonic visual system.
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.
authors.affiliation: Department 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.
authors.forename: Cláudio Gouveia
authors.initials: CG
authors.lastname: Roque
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK.
authors.forename: Hovy Ho-Wai
authors.initials: HH
authors.lastname: Wong
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK.
authors.forename: Julie Qiaojin
authors.initials: JQ
authors.lastname: Lin
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK ceh33@cam.ac.uk.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Holt
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001757:Blastomeres / Q000166:cytology; D002478:Cells, Cultured; D004625:Embryo, Nonmammalian / Q000196:embryology; D020287:In Situ Nick-End Labeling; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008928:Mitochondria / Q000502:physiology; D063154:Mitochondrial Dynamics / Q000235:genetics; D060172:Morpholinos / Q000235:genetics; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology; D009899:Optic Lobe, Nonmammalian / Q000196:embryology*; D051381:Rats; D011916:Rats, Inbred F344; D012160:Retina / Q000196:embryology*; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000378:metabolism; D000090324:Tumor Protein, Translationally-Controlled 1; D014795:Visual Pathways / Q000196:embryology* / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D014408:Biomarkers, Tumor; D060172:Morpholinos; D064549:Myeloid Cell Leukemia Sequence 1 Protein; C000715649:Tpt1 protein, rat; D000090324:Tumor Protein, Translationally-Controlled 1
keywords: Axon guidance; Neural circuitry assembly; RNA localisation; Retinal ganglion cell; Retinotectal projection; Tctp; tpt1