The expression of teneurin-4 in the avian embryo: potential roles in patterning of the limb and nervous system

Abstract

Teneurins are type II transmembrane proteins that play important roles in pattern formation in Drosophila, axon fasciculation and organogenesis in Caenorhabidits elegans, and neuronal pathfinding in the visual system of the mouse. There is evidence that a peptide derived from a proteolytic event near the C-terminus of teneurins leads to formation of an active neuropeptide, while processing at and near the transmembrane domain leads to shedding of the extracellular domain into the extracellular matrix and the generation of an intracellular fragment that is transported to the nucleus. In vertebrates there are four teneurins. Here, we have studied the expression of teneurin-4 in the chicken embryo. An antiserum against part of the intracellular domain of teneurin-4 recognizes several low molecular weight bands on immunoblots of embryonic chicken brain homogenates, indicating that teneurin-4 is likely to be processed at one or more predicted proteolytic cleavage sites. Antisera against the EGF-like repeats of the extracellular domain label some mesenchyme in the early embryo, and near basement membranes this labeling partially overlaps with anti-laminin (gamma 1 chain) immunostaining. At embryonic day 7, anti-teneurin-4 labels bundles of axons in the nasal, but not temporal retina. Later in development, retinal expression switches so that teneurin-4 is found in the temporal, but not nasal, ganglion cell layer. Teneurin-4 immunolocalization was also compared with other teneurins in the developing limb, where each teneurin is expressed in distinctive regions. These patterns of expression suggest roles for teneurin-4 in patterning and neuronal pathfinding in the avian embryo.

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

“…In different cell lines, siRNAs reduced Ten-2 and Ten-4 mRNA levels by 80–85% and by 70–90%, respectively, which however did not cause consistent effects on the expression of BCL2, BIRC5, CASP3, and CASP8 (S9 Fig). Similarly, VEGF mRNA levels were not significantly altered, although a potential role of Ten-4 in angiogenesis was previously suggested based on its immunolocalization in coronary and tumor blood vessels [45,46]. In contrast, we consistently measured a ∼20% increase in proliferation at 72 h in MCF7 and BT474 cells treated with Ten-4-specific siRNA, with the latter achieving significance (P = .0024, parametric comparison of independent means) (Fig 8A).…”

Teneurin-3 Specifies Morphological and Functional Connectivity of Retinal Ganglion Cells in the Vertebrate Visual System

“…Previous studies in mice showed that Teneurin-3 regulates the development of topography in the retinogeniculate (Leamey et al., 2007) and retinocollicular pathways (Dharmaratne et al., 2012), specifically for the ipsilaterally projecting RGC population. However, the fact that teneurin-3 is not exclusively expressed in ipsilaterally projecting RGCs (Leamey et al., 2007) and is also found in the visual system of species where RGCs project contralaterally only, like chick (Kenzelmann-Broz et al., 2010) and zebrafish (Mieda et al., 1999; this study), clearly suggests additional functions in vertebrate visual system development.…”

Regulation of conduction time along axons

“…Moreover, oligodendrocytes are electrically active as well (Káradóttir et al, 2008) and their membrane potential can influence conduction velocity (Yamazaki et al, 2007). Recently, Teneurin-4 has been identified as a regulator of oligodendrocyte differentiation and myelination (Suzuki et al, 2012) and, as it is expressed in the auditory brainstem, it might play a role in functional myelination (Kenzelmann-Broz et al, 2010). …”