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The DNA-binding protein TRF2 is essential for telomere protection and chromosome stability in mammals. We show here that TRF2 expression is activated by the Wnt/b-catenin signalling pathway in human cancer and normal cells as well as in mouse intestinal tissues. Furthermore, b-catenin binds to TRF2 gene regulatory regions that are functional in a luciferase transactivating assay. Reduced b-catenin expression in cancer cells triggers a marked increase in telomere dysfunction, which can be reversed by TRF2 overexpression. We conclude that the Wnt/b-catenin signalling pathway maintains a level of TRF2 critical for telomere protection. This is expected to have an important role during development, adult stem cell function and oncogenesis.

The thyroid hormones control the development and the homeostasis of several organs in vertebrates. Their actions depend, for the most part, on nuclear receptors, the TRs, which are transcription factors whose activity is modulated by the hormone T3. The gastrointestinal tract is a well characterized target of thyroid hormones and TRs, as extensively described in the literature. In fact, its remodeling in amphibians during thyroid hormone-dependent metamorphosis is well characterized at the cellular and the molecular levels. However, whereas a great attention has been paid to the nervous system and to cardiac development and physiology, the function of thyroid hormones and TRs in the mammalian gastrointestinal tract has been, until recently, underestimated. Several studies have described an important conservation of this hormonal signal during intestinal development and have suggested that it may play a role in stem cell physiology in both amphibians and mammals. These findings show the importance of the thyroid hormones and TRs, whose homologous actions are maintained across species. In the present review, we summarize the most recent data on this issue, starting from work that has been conducted on amphibian metamorphosis to results on postnatal development, homeostasis, and tumorigenesis in mammals. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease.

Dmrt genes encode a large family of transcription factors characterized by the presence of a DM domain, an unusual zinc finger DNA binding domain. While Dmrt genes are well known for their important role in sexual development in arthropodes, nematodes and vertebrates, several new findings indicate emerging functions of this gene family in other developmental processes. Here, we provide an overview of the evolution, structure and mechanisms of action of Dmrt genes. We summarize recent findings on their function in sexual regulation and discuss more extensively the role played by these proteins in somitogenesis and neural development.

The thyroid hormones, T3 and T4, control several developmental and homeostatic processes. From a molecular point of view, most of their actions depend on the activity of the thyroid hormone nuclear receptors (TRs), which are T3-modulated transcription factors. Recent studies have not only highlighted that the physiological response induced by T3 within a cell depends on the expression of specific TRs, but also that the functions of TRs are coordinated by and integrated in other signalling pathways. This is particularly the case for the multilevel interactions between TRs and the Wnt signalling pathway. Interestingly both signals are involved in development and homeostasis, and their alterations are responsible for the development of pathologies, such as cancer. Here, we present findings on the complex crosstalk between TRs and Wnt in several organisms and in different tissue contexts, and speculate on the biological relevance of modulating TR-Wnt functionality in therapeutic approaches aimed to target cancer cells or applications for regenerative medicine.

The Dmrt (doublesex and mab-3 related transcription factor) genes encode a large family of evolutionarily conserved transcription factors whose function in sex specific differentiation has been well studied in all animal lineages. In vertebrates, their function is not restricted to the developing gonads. For example, Xenopus Dmrt4 is essential for neurogenesis in the olfactory system. Here we have isolated and characterized Xenopus Dmrt5 and found that it is coexpressed with Dmrt4 in the developing olfactory placodes. As Dmrt4, Dmrt5 is positively regulated in the ectoderm by neural inducers and negatively by proneural factors. Both Dmrt5 and Dmrt4 genes are also activated by the combined action of the transcription factor Otx2, broadly transcribed in the head ectoderm and of Notch signaling, activated in the anterior neural ridge. As for Dmrt4, knockdown of Dmrt5 impairs neurogenesis in the embryonic olfactory system and in neuralized animal caps. Conversely, its overexpression promotes neuronal differentiation in animal caps, a property that requires the conserved C-terminal DMA and DMB domains. We also found that the sea anenome Dmrt4/5 related gene NvDmrtb also induces neurogenesis in Xenopus animal caps and that conversely, its knockdown in Nematostella reduces elav-1 positive neurons. Together, our data identify Dmrt5 as a novel important regulator of neurogenesis whose function overlaps with that of Dmrt4 during Xenopus olfactory system development. They also suggest that Dmrt may have had a role in neurogenesis in the last common ancestor of cnidarians and bilaterians.

Background: Quantitative real-time polymerase chain reaction (RT-qPCR) is valuable for studying the molecular events underlying physiological and behavioral phenomena. Normalization of real-time PCR data is critical for a reliable mRNA quantification. Here we identify reference genes to be utilized in RT-qPCR experiments to normalize and monitor the expression of target genes in the brain of the cephalopod mollusc Octopus vulgaris, an invertebrate. Such an approach is novel for this taxon and of advantage in future experiments given the complexity of the behavioral repertoire of this species when compared with its relatively simple neural organization.

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