The expression and activity of β-catenin in the thalamus and its projections to the cerebral cortex in the mouse embryo

Abstract

BackgroundThe mammalian thalamus relays sensory information from the periphery to the cerebral cortex for cognitive processing via the thalamocortical tract. The thalamocortical tract forms during embryonic development controlled by mechanisms that are not fully understood. β-catenin is a nuclear and cytosolic protein that transduces signals from secreted signaling molecules to regulate both cell motility via the cytoskeleton and gene expression in the nucleus. In this study we tested whether β-catenin is likely to play a role in thalamocortical connectivity by examining its expression and activity in developing thalamic neurons and their axons.ResultsAt embryonic day (E)15.5, the time when thalamocortical axonal projections are forming, we found that the thalamus is a site of particularly high β-catenin mRNA and protein expression. As well as being expressed at high levels in thalamic cell bodies, β-catenin protein is enriched in the axons and growth cones of thalamic axons and its growth cone concentration is sensitive to Netrin-1. Using mice carrying the β-catenin reporter BAT-gal we find high levels of reporter activity in the thalamus. Further, Netrin-1 induces BAT-gal reporter expression and upregulates levels of endogenous transcripts encoding β-actin and L1 proteins in cultured thalamic cells. We found that β-catenin mRNA is enriched in thalamic axons and its 3'UTR is phylogenetically conserved and is able to direct heterologous mRNAs along the thalamic axon, where they can be translated.ConclusionWe provide evidence that β-catenin protein is likely to be an important player in thalamocortcial development. It is abundant both in the nucleus and in the growth cones of post-mitotic thalamic cells during the development of thalamocortical connectivity and β-catenin mRNA is targeted to thalamic axons and growth cones where it could potentially be translated. β-catenin is involved in transducing the Netrin-1 signal to thalamic cells suggesting a mechanism by which Netrin-1 guides thalamocortical development.

Axonal Translation of β-Catenin Regulates Synaptic Vesicle Dynamics

“…How local β-catenin translation is regulated remains unknown, although the absence of postsynaptic targets in our model system suggests an autonomous presynaptic signal (Andreae et al, 2012). Recent evidence supports the involvement of target-derived signals including netrin and NT3 in the local translation of β-catenin in thalamic axons (Pratt et al, 2012) and during the initial outgrowth of hippocampal axons (Kundel et al, 2009). The netrin receptor, DCC, has been reported to anchor translational machinery and the clustering of DCC in the absence of netrin may induce low levels of translation (Tcherkezian et al, 2010).…”

Wnt/β‐catenin signaling in brain development and mental disorders: keeping TCF7L2 in mind

“…Abundant expression of Tcf7l2 and Lef1 was specifically observed during postmitotic development and in adulthood in the thalamus, habenula, and some midbrain structures in vertebrates, including primates . These TCF7L2‐positive brain regions exhibited massive nuclear β‐catenin accumulation , and high reporter gene activity in Wnt reporter mice . This accumulation appears to be independent of the upstream components of the Wnt signaling, but dependent of TCF7L2.…”

Regulation of Neuronal Gene Expression by Local Axonal Translation

“…The opposing roles of locally translated CaMKII and cdk5 in the regulation of vesicles suggest that distinct signals may employ translational programs that include one or the other. Although the endogenous signals that regulate presynaptic translation in the vertebrate nervous system have not been well-characterized, it is of note that netrin regulates axonal β-catenin translation during outgrowth in both hippocampal and thalamocortical axons (62,63). The cues that regulate local presynaptic translation may thus be broadly conserved in both Aplysia and mammals.…”