Tumor protein Tctp regulates axon development in the embryonic visual system

Development
Cláudio Gouveia RoqueC E Holt

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.

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Citations

Feb 15, 2020·Wiley Interdisciplinary Reviews. RNA·Nicolai von Kügelgen, Marina Chekulaeva
Mar 7, 2020·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Elena SenaBéatrice C Durand
Jul 11, 2020·Cells·Ulrich-Axel Bommer, Adam Telerman
Sep 30, 2020·RNA Biology·Julie Qiaojin LinChristine E Holt
Nov 22, 2018·Frontiers in Molecular Neuroscience·Cláudio Gouveia Roque, Christine E Holt
Sep 27, 2018·Frontiers in Cellular Neuroscience·Kin-Mei LeungChristine E Holt
May 24, 2020·International Journal of Molecular Sciences·Sung Wook Kim, Kyong-Tai Kim
Nov 21, 2020·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Géraldine BossardAnne Geiger

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Methods Mentioned

BETA
laser-capture microdissection
reverse transcription PCR
PCR
GTPase
1
proximity ligation assay
confocal microscopy
proximity ligation

Software Mentioned

qbase
GraphPad
Prism
Biogazelle
GeneTools
geNorm

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