Expression and Roles of Teneurins in Zebrafish

Abstract

The teneurins, also known as Ten-m/Odz, are highly conserved type II transmembrane glycoproteins widely expressed throughout the nervous system. Functioning as dimers, these large cell-surface adhesion proteins play a key role in regulating neurodevelopmental processes such as axon targeting, synaptogenesis and neuronal wiring. Synaptic specificity is driven by molecular interactions, which can occur either in a trans-homophilic manner between teneurins or through a trans-heterophilic interaction across the synaptic cleft between teneurins and other cell-adhesion molecules, such as latrophilins. The significance of teneurins interactions during development is reflected in the widespread expression pattern of the four existing paralogs across interconnected regions of the nervous system, which we demonstrate here via in situ hybridization and the generation of transgenic BAC reporter lines in zebrafish. Focusing on the visual system, we will also highlight the recent developments that have been made in furthering our understanding of teneurin interactions and their functionality, including the instructive role of teneurin-3 in specifying the functional wiring of distinct amacrine and retinal ganglion cells in the vertebrate visual system underlying a particular functionality. Based on the distinct expression pattern of all teneurins in different retinal cells, it is conceivable that the combination of different teneurins is crucial for the generation of discrete visual circuits. Finally, mutations in all four human teneurin genes have been linked to several types of neurodevelopmental disorders. The opportunity therefore arises that findings about the roles of zebrafish teneurins or their orthologs in other species shed light on the molecular mechanisms in the etiology of such human disorders.

Mapping epigenetic divergence in the massive radiation of Lake Malawi cichlid fishes

“…tenm2 is a gene expressed early on during zebrafish embryogenesis as well as in cichlid brain and embryo (Supplementary Fig. 11h), and is involved in neurodevelopment and neuron migration-related cell signalling 56 . This 2.7kbp-long DMR is completely unmethylated in the algae-eating rock-dweller Petrotilapia genalutea (almost 80% reduction of methylation overall compared to the other species) and may mediate species-specific adaptive phenotypic plasticity related to synapse formation and neuronal networks.…”

Analysis of Homozygous-by-Descent (HBD) Segments for Purebred and Crossbred Pigs in Russia

“…Studies have also shown that NEDD4 acts as an E3 ligase and regulates the embryonic development and growth of animals (proliferation, autophagy and differentiation of multiple malignancies) [ 35 ]. The TENM3 gene encodes highly conservative transmembrane glycoproteins of type II that are widely expressed in the nervous system and play a key role in regulating the development of the nervous system [ 36 ]. Feldman et al [ 37 ] proposed that mutations in the TENM3 gene in humans and mice lead to a slowdown of chondrogenes.…”

Teneurins: Mediators of Complex Neural Circuit Assembly in Mammals

“…In the chick visual system, for example, Ten-m1 and Ten-m2 were found to be differentially expressed by the tectofugal and thalamofugal pathways, respectively (Rubin et al, 1999, 2002). Dynamic and differential, but partially overlapping, expression patterns have also been observed in the nervous system of zebrafish, with particularly strong expression of Ten-m3 and Ten-m4 (Mieda et al, 1999; Cheung et al, 2019). In this species, expression of Ten-m3 in the amacrine and ganglion cells of the developing retina is important for the formation of intraretinal circuitry (Antinucci et al, 2013, 2016).…”

“…While the Ten-ms clearly play an important role in the formation of binocular visual circuits in mice, it should be pointed out that they are also expressed in the visual pathway of zebrafish and chicks (Rubin et al, 1999, 2002; Antinucci et al, 2013; Cheung et al, 2019), species which have little or no ipsilateral retinal projection. In zebrafish, which have entirely crossed retinal projections and lack binocular overlap, Ten-m3 has been shown to contribute to the specification of RGC connectivity and function (Antinucci et al, 2013, 2016), consistent with its role as a homophilic adhesion molecule.…”

“…One of the more recent entrants to this stage is the teneurins. In a range of different species and brain circuits, these molecules were found to exhibit distributions across afferent and target fields which pointed to the idea that they may indeed help to determine patterns of neural connectivity (e.g., Rubin et al, 1999, 2002; Zhou et al, 2003; Li et al, 2006; Leamey et al, 2008; Carr et al, 2013, 2014; Bibollet-Bahena et al, 2017; Cheung et al, 2019). Over recent years, genetically modified mice have been generated which have enabled these ideas to be tested in vivo .…”