Teneurins: A conserved family of transmembrane proteins involved in intercellular signaling during development

Department of Cell Biology and Human Anatomy, University of California at Davis, Davis, CA 95616, USA.
Developmental Biology (Impact Factor: 3.55). 03/2006; 290(2):237-45. DOI: 10.1016/j.ydbio.2005.11.038
Source: PubMed


Teneurins, which were initially described as ten-a and the pair-rule gene ten-m/odz in Drosophila, are a family of highly conserved proteins that have recently been characterized in Caenorhabditis elegans and a number of vertebrates. We have proposed the nomenclature teneurin 1-4 for the four members of this gene family found in vertebrates. Recent evidence shows that teneurins belong to a novel class of signaling molecules that function both at the cell surface as type II transmembrane receptors and, after the release of the intracellular domain, as transcriptional regulators. Nuclear localization of the intracellular domain has been observed in vitro in mammalian cells and confirmed in vivo in C. elegans. RNAi studies and mutational analysis has revealed that Ten-1 in C. elegans is an important regulator of many aspects of morphogenesis, including germ cell development and neuronal pathfinding. In vertebrates, teneurins are concentrated in the developing and adult central nervous system and at sites of pattern formation, including the developing limb. Teneurins also possess a carboxy terminal sequence that may be processed to generate a neuromodulatory peptide. Teneurin function appears to be required for a fundamentally important signaling mechanism conserved between invertebrates and vertebrates having an impact on many processes relying on cell-cell contact throughout development.

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    • "Teneurin proteins are proposed to regulate gene expression in the nervous system during development [14]. TEMN2 is involved in development of neuronal circuits in the visual system [15] and has been shown to be expressed in the developing limbs, somites, and craniofacial mesenchyme [16]. "
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    ABSTRACT: Life at high altitude results in physiological and metabolic challenges that put strong evolutionary pressure on performance due to oxidative stress, UV radiation and other factors dependent on the natural history of the species. To look for genes involved in altitude adaptation in a large herbivore, this study explored genome differentiation between a feral population of Andean horses introduced by the Spanish in the 1500s to the high Andes and their Iberian breed relatives. Using allelic genetic models and Fst analyses of ~50 K single nucleotide polymorphisms (SNPs) across the horse genome, 131 candidate genes for altitude adaptation were revealed (Bonferoni of p <= 2 x 10-7). Significant signals included the EPAS1 in the hypoxia-induction-pathway (HIF) that was previously discovered in human studies (p = 9.27 x 10-8); validating the approach and emphasizing the importance of this gene to hypoxia adaptation. Strong signals in the cytochrome P450 3A gene family (p = 1.5 x10-8) indicate that other factors, such as highly endemic vegetation in altitude environments are also important in adaptation. Signals in tenuerin 2 (TENM2, p = 7.9 x 10-14) along with several other genes in the nervous system (gene categories representation p = 5.1 x 10-5) indicate the nervous system is important in altitude adaptation. In this study of a large introduced herbivore, it becomes apparent that some gene pathways, such as the HIF pathway are universally important for high altitude adaptation in mammals, but several others may be selected upon based on the natural history of a species and the unique ecology of the altitude environment.
    Full-text · Article · Dec 2013 · BMC Evolutionary Biology
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    • "Tenm4, teneurin transmembrane protein 4, is a mouse homolog of the Drosophila gene tenascin major (Ten-m), also called Odd oz (Odz) [9-11], which was originally associated with segmentation defects. Ten-m is a member of the Teneurin protein family and encodes a transmembrane protein with tenascin-like EGF (epidermal growth factor) repeats. "
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    ABSTRACT: Background Tenm4 is a mouse homolog of the Drosophila gene Tenascin-m (Ten-m (Odd oz)), which functions in motor neuron routing. Recently, a genome-wide association analysis for bipolar disorder identified a new susceptibility locus at TENM4 increasing the importance of understanding Tenm4. A series of Tenm4 mouse alleles showing a broad range of phenotypes were isolated after ENU mutagenesis. Here, we examine the timing and features of gastrulation failure in a loss of function allele. Results Embryonic mesoderm did not form in loss of function Tenm4m1/m1 mutant embryos. Genes normally expressed in embryonic mesoderm were not expressed in the mutant, the primitive streak did not form, and markers of the anteroposterior axis were not expressed or were mislocalized. The lack of embryonic mesoderm could not be attributed to poor proliferation of the epiblast, as normal numbers of dividing cells were observed. Epiblast cells maintained expression of Pou5f1 suggesting that they remain pluripotent, but they did not have the capacity to form any germ layer derivatives in teratomas, showing that the inability to induce mesoderm is cell autonomous. Misexpression of E-cadherin and N-cadherin suggest that the embryos did not undergo an epithelial-to-mesenchymal transition. In addition, Wnt signaling did not occur in the mutants, as assessed by the TOPGAL reporter assay, while a GSK3β inhibitor partially rescued the mutant embryos, and rescued TOPGAL reporter expression. Conclusions These data demonstrate that Tenm4 mutants fail to form a primitive streak and to induce embryonic mesoderm. Markers of anterior posterior patterning fail to be expressed or are mislocalized. Further, Tenm4 mutants lack the ability to differentiate in a cell autonomous manner. Together, our data suggest that embryos become impaired prior to E6.5 and as a result, Wnt signaling fails to occur; however, the involvement of other signaling pathways remains to be examined.
    Full-text · Article · Mar 2013 · BMC Developmental Biology
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    • "The Odz family belongs to a type II transmembrane protein family that possesses a C-terminal extracellular domain, transmembrane region, and intracellular domain. Three postulated protease cleavage sites exist in the extraand transmembrane domains of Odzs (Tucker and Chiquet- Ehrismann 2006). Functional studies of Drosophila indicated that Odz functions as a pair-rule gene (Levine et al. 1994). "
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    ABSTRACT: Satellite cells, muscle-specific stem cells, are anatomically identified as the mononuclear cells residing external to the myofiber plasma membrane and beneath the basal lamina. Skeletal muscle has great regenerative potential, and the regeneration process depends absolutely on satellite cells. In uninjured muscle, satellite cells are maintained in a quiescent state, and some genes are expressed in a quiescent-specific manner. Here we show that Odz4/Ten-m4, a mouse homolog of the Drosophila pair-rule gene odd Oz (odz or Ten-m), is expressed in quiescent satellite cells on the protein level, but not in activated/proliferating myoblasts. Intriguingly, the timing of the reappearance of Odz4 and calcitonin receptor (another quiescence molecule) on Pax7-positive cells was different during the regeneration process. In addition, almost all neonatal satellite cells express Odz4, but only some of them express calcitonin receptor. These results indicate that Odz4 may be useful as a new marker of satellite cells and that quiescence molecules are differently expressed in regenerating and neonatal muscle.
    Full-text · Article · May 2012 · Journal of molecular histology
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