Expression of Wnt signaling skeletal development genes in the cartilaginous fish, elephant shark (Callorhinchus milii).

Jawed vertebrates (Gnasthostomes) are broadly separated into cartilaginous fishes (Chondricthyes) and bony vertebrates (Osteichthyes). Cartilaginous fishes are divided into chimaeras (e.g. ratfish, rabbit fish and elephant shark) and elasmobranchs (e.g. sharks, rays and skates). Both cartilaginous fish and bony vertebrates are believed to have a common armoured bony ancestor (Class Placodermi), however cartilaginous fish are believed to have lost bone. This study has identified and investigated genes involved in skeletal development in vertebrates, in the cartilaginous fish, elephant shark (Callorhinchus milii). Ctnnb1 (ß-catenin), Sfrp (secreted frizzled protein) and a single Sost or Sostdc1 gene (sclerostin or sclerostin domain-containing protein 1) were identified in the elephant shark genome and found to be expressed in a number of tissues, including cartilage. ß-catenin was also localized in several elephant shark tissues. The expression of these genes, which belong to the Wnt/ß-catenin pathway, is required for normal bone formation in mammals. These findings in the cartilaginous skeleton of elephant shark support the hypothesis that the common ancestor of cartilaginous fishes and bony vertebrates had the potential for making bone.

Evolution of the parathyroid hormone family and skeletal formation pathways.

Bone is considered to be a feature of higher vertebrates and one of the features that was required for the movement from water onto land. But there are a number of evolutionarily important species that have cartilaginous skeletons, including sharks. Both bony and cartilaginous fish are believed to have a common ancestor who had a bony skeleton. A number of factors and pathways have been shown to be involved in the development and maintenance of bony skeleton including the Wnt pathway and the parathyroid hormone gene family. The study of these pathways and factors in cartilaginous animals may shed light on the evolution of the vertebrate skeleton.

Transport of thyroid hormones via the choroid plexus into the brain: the roles of transthyretin and thyroid hormone transmembrane transporters.

Thyroid hormones are key players in regulating brain development. Thus, transfer of appropriate quantities of thyroid hormones from the blood into the brain at specific stages of development is critical. The choroid plexus forms the blood-cerebrospinal fluid barrier. In reptiles, birds and mammals, the main protein synthesized and secreted by the choroid plexus is a thyroid hormone distributor protein: transthyretin. This transthyretin is secreted into the cerebrospinal fluid and moves thyroid hormones from the blood into the cerebrospinal fluid. Maximal transthyretin synthesis in the choroid plexus occurs just prior to the period of rapid brain growth, suggesting that choroid plexus-derived transthyretin moves thyroid hormones from blood into cerebrospinal fluid just prior to when thyroid hormones are required for rapid brain growth. The structure of transthyretin has been highly conserved, implying strong selection pressure and an important function. In mammals, transthyretin binds T4 (precursor form of thyroid hormone) with higher affinity than T3 (active form of thyroid hormone). In all other vertebrates, transthyretin binds T3 with higher affinity than T4. As mammals are the exception, we should not base our thinking about the role of transthyretin in the choroid plexus solely on mammalian data. Thyroid hormone transmembrane transporters are involved in moving thyroid hormones into and out of cells and have been identified in many tissues, including the choroid plexus. Thyroid hormones enter the choroid plexus via thyroid hormone transmembrane transporters and leave the choroid plexus to enter the cerebrospinal fluid via either thyroid hormone transmembrane transporters or via choroid plexus-derived transthyretin secreted into the cerebrospinal fluid. The quantitative contribution of each route during development remains to be elucidated. This is part of a review series on ontogeny and phylogeny of brain barrier mechanisms.