The glycoprotein Ten‐m3 mediates topography and patterning of thalamostriatal projections from the parafascicular nucleus in mice

Abstract

The striatum is the key input nucleus of the basal ganglia, and is implicated in motor control and learning. Despite the importance of striatal circuits, the mechanisms associated with their development are not well established. Previously, Ten-m3, a member of the Ten-m/teneurin/odz family of transmembrane glycoproteins, was found to be important in the mapping of binocular visual pathways. Here, we investigated a potential role for Ten-m3 in striatal circuit formation. In situ hybridisation revealed a patchy distribution of Ten-m3 mRNA expression superimposed on a high-dorsal to low-ventral gradient in a subregion of the striatal matrix. A survey of afferent/efferent structures associated with the matrix identified the parafascicular thalamic nucleus (PF) as a potential locus of action. Ten-m3 was also found to be expressed in a high-dorsal to low-ventral gradient in the PF, corresponding topographically to its expression in the striatum. Further, a subset of thalamic terminal clusters overlapped with Ten-m3-positive domains within the striatal matrix. Studies in wild-type (WT) and Ten-m3 knockout (KO) mice revealed no differences in overall striatal or PF structure. Thalamostriatal terminals in KOs, however, while still confined to the matrix subregion, lost their clustered appearance. Topography was also altered, with terminals from the lateral PF projecting ectopically to ventral and medial striatum, rather than remaining confined dorsolaterally as in WTs. Behaviorally, Ten-m3 KOs displayed delayed motor skill acquisition. This study demonstrates that Ten-m3 plays a key role in directing the formation of thalamostriatal circuitry, the first molecular candidate reported to regulate connectivity within this pathway.

Expression of teneurins is associated with tumor differentiation and patient survival in ovarian cancer

“…The role of Teneurins in neuronal development has been vastly documented [48–50], but their appearance in the field of oncology is recent and their phenotypic contribution to tumorigenesis and malignant progression is unclear. We previously identified Ten-2 as a potential biomarker for malignant mesothelioma [25], and found evidence for dysregulated expression of Ten-2 and Ten-4 in other cancers through search of in the literature and by mining transcriptomics datasets [24].…”

Environmental Enrichment Rescues Visually-Mediated Behavior in Ten-m3 Knockout Mice During an Early Critical Period

“…While vision is clearly important for being able to detect the looming stimulus, the reduced latency of standard-housed KOs could also be due to other deficits which may also be ameliorated by EE from birth. We have previously shown that although quite mobile (Leamey et al, 2007), Ten-m3 KOs exhibit subtle deficits in motor learning (Tran et al, 2015) as well as kyphosis (Leamey et al, 2007). The increased latency to escape observed in KOs could, therefore, be a result of reduced motor ability.…”

A dual-strategy expression screen for candidate connectivity labels in the developing thalamus

“…Roles for Odz2 and Odz3 have been demonstrated in establishing the topography and segregation of ipsilateral and contralateral afferents in the dLGN and of thalamic afferents in visual cortex (reviewed in [35]). More recently, Odz3 has also been shown to control topography of thalamostriatal projections [13]. …”

“…Many of these, including Ephrins/Eph-receptors, Netrins/DCC/Unc5s, Slits/Robos, Neuregulin-1/Erbb4, secreted semaphorins/ neuropilins and L1 cell adhesion molecules, mediate general processes such as avoidance of the hypothalamus, projection into the internal capsule and topographic organisation of thalamocortical and/or corticothalamic projections through this intermediate target region (reviewed in [8, 9]). By contrast, very few molecules have been found so far that mediate more specific connectivity relationships of particular thalamic nuclei, such as Cdh6 [10], or that control sub-organisation of projections within thalamic nuclei, such as Lrp8 [11] or Ten-m3/Odz3 [12], which also regulates topography of projections to striatum [13]. …”