Teneurins: Mediators of Complex Neural Circuit Assembly in Mammals

Abstract

The teneurins (Ten-m/Odz) are a family of evolutionarily ancient transmembrane molecules whose complex and multi-faceted roles in the generation of mammalian neural circuits are only beginning to be appreciated. In mammals there are four family members (Ten-m1-4). Initial expression studies in vertebrates revealed intriguing expression patterns in interconnected populations of neurons. These observations, together with biochemical and over-expression studies, led to the hypothesis that homophilic interactions between teneurins on afferent and target cells may help to guide the assembly of neural circuits. This review will focus on insights gained on teneurin function in vivo in mammals using mouse knockout models. These studies provide support for the hypothesis that homophilic interactions between teneurin molecules can guide the formation of neural connections with largely consistent results obtained in hippocampal and striatal circuits. Mapping changes obtained in the mouse visual pathway, however, suggest additional roles for these glycoproteins in the formation and specification of circuits which subserve binocular vision.

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

“…The hippocampus is well-known for its important roles in spatial learning and navigation (reviewed in Moser et al, 2017;Rolls, 2018). Ten-m3 is highly expressed in the hippocampus (Zhou et al, 2003;Leamey et al, 2008), and hippocampal connectivity is impacted in standard-housed Ten-m3 KOs (Berns et al, 2018;Leamey and Sawatari, 2019). While there were no apparent differences in the exploration of the arena in the pre-stimulus interval, or awareness of the presence of the shelter, we cannot rule out the possibility that defects in spatial navigation could have influenced the performance of the standard-housed Ten-m3 KO mice.…”

“…The early visual pathway of Ten-m3 knockout (KO) mice provides an excellent model to explore this issue. Ten-m3 belongs to a family of type II transmembrane proteins which have been shown to regulate a number of developmental processes such axonal guidance, synapse formation and dendritic structure (Leamey et al, 2007;Young and Leamey, 2009;Dharmaratne et al, 2012;Hong et al, 2012;Mosca et al, 2012;Antinucci et al, 2013Antinucci et al, , 2016Young et al, 2013;Glendining et al, 2017;Berns et al, 2018;Leamey and Sawatari, 2019). Most notably for this project, the phenotype of Ten-m3 KO mice is characterized by a highly stereotyped miswiring of ipsilateral retinal projections within the dorsal lateral geniculate nucleus (dLGN; Leamey et al, 2007).…”

Human HINT1 Mutant Proteins that Cause Axonal Motor Neuropathy Exhibit Anomalous Interactions with Partner Proteins

“…HINT1 couples with ICD teneurin 1, which acts as a transcription factor in the nucleus [18]. Teneurins (four members in humans, Ten1-4) promote neurite outgrowth, cell adhesion, dendritic morphology, axonal guidance and synapse formation [37]. The two teneurins present in Drosophila, Tenm and Ten-a, regulate neuromuscular synapse organization and target selection [38].…”

The ALS-Related σ1R E102Q Mutant Eludes Ligand Control and Exhibits Anomalous Response to Calcium

“…HINT1 couples with the intracellular domain of teneurin 1, which acts as a transcription factor in the nucleus [ 42 ]. The teneurin family (four members in humans, Ten1–4) promotes neurite outgrowth, cell adhesion, dendritic morphology, axonal guidance, and synapse formation and regulates neuromuscular synapse organization and target selection [ 39 , 43 ]. Mutations in the human TEN4 gene are associated with essential tremor movement disorder in patients [ 44 ].…”