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The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crests (NCSCs) might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSCs). In this paper, we will review all information available concerning NCSC from adult tissues and their possible use in regenerative medicine. Moreover, as multiple recent studies showed the beneficial effect of bone marrow stromal cells in neurodegenerative diseases, we will discuss which stem cells isolated from adult bone marrow should be more suitable for cell replacement therapy.

Ecdysteroid hormones have been shown to regulate growth and development in insects, chelicerates and crustaceans. While they presumably mediate analogous functions in all arthropods, their action outside Insecta is poorly understood. Ecdysteroid receptors are heterodimeric proteins composed of two nuclear receptor superfamily members, the ecdysone receptor (EcR) and Ultraspiracle (USP), the invertebrate homologue of retinoid x receptors (RXRs). When paired, EcR/USP dimers function as ligand-activated transcription factors, binding to DNA response elements in target genes and activating transcription. A curious feature of the insect EcR and USP homologues isolated to date is the striking degree of heterogeneity in both EcR and USP proteins, relative to vertebrate nuclear receptor homologues. This feature has raised a number of questions regarding their evolution and functional equivalence. To examine the question of ecdysteroid action in ixodid ticks, we isolated chelicerate EcR and RXR homologues from the ixodid tick, Amblyomma americanum. Like insects, ticks possess a single EcR homologue that encodes multiple protein isoforms. However, ticks possess at least two RXR genes that encode proteins with greater overall similarity to vertebrate RXRs. While tick EcR and RXR proteins can partner to form functional ecdysteroid receptors, the DNA and ligand binding domains of tick EcR and RXR proteins are quite divergent, and suggest that there may be important functional differences in both DNA and ligand binding of tick ecdysteroid receptors.

The nuclear receptor (NR) superfamily includes, in addition to ligandactivated transcription factors, members called orphan receptors, for which no ligand has yet been identified. Phylogenetic analysis shows that the nuclear receptor superfamily can be split into six subfamilies. Interestingly, there appears to be no relationship between the position of a given liganded receptor in the tree and the chemical nature of its ligand. For example, RAR and RXR, which both recognize retinoids, belong to two different subfamilies, suggesting an independence between the evolutionary history of the receptors and their ligand binding abilities. A PCR screen for the presence of NR genes in several phyla of early- and nonmetazoan organisms suggests that NR are specific to metazoans and also reveals that the NR genes in Hydra or Anemonia appear to be limited to homologues of orphan receptors. Taken together these data suggest that the first members of the superfamily were probably orphan receptors that later on gained the ability to bind a ligand. Finally, we observed that SmFTZ-F1 and SmRXR are expressed at different levels along the life cycle of the parasitic flatworm Schistosoma mansoni. This suggests that these receptors may play a role in the control of the development of this organism.

The thyroid hormone receptor α (THRA or c-erbA-1) gene belongs to a family of genes which encode nuclear receptors for various hydrophobic ligands such as steroids, vitamin D, retinoic acid and thyroid hormones. These receptors are composed of several domains important for hormone-binding, DNA-binding, dimerization and activation of transcription. We show here that the human THRA gene is organized in 10 exons distributed along 27 kbp of genomic DNA on chromosome 17. The position of the Introns in human THRA is highly conserved when compared to the chicken gene despite their differing lengths. The N-terminal A/B domain as well as the 5′ untranslated region is encoded by two exons. Interestingly, each of the putative zinc fingers of the receptors DNA-binding domain is encoded by one exon and the hormonebinding domain is encoded by one exon and the hormonebinding domain is assembled from three exons. The two exons of the gene are alternatively spliced to generate two different messenger RNAs. In addition, we confirm that another gene, belonging to the nuclear receptor superfamily, ear-1, overlaps with the 3′ region of THRA in an opposite transcriptional orlentation.

The HMG box Is a novel type of DNA-blndlng domain found in a diverse group of proteins. The HMG box superfamily comprises a.o. the High Mobility Group proteins HMG1 and HMG2, the nucleolar transcription factor UBF, the lymphoid transcription factors TCF-1 and LEF-1, the fungal mating-type genes mat-Mc and MATA1, and the mammalian sex-determining gene SRY. The superfamily dates back to at least 1,000 million years ago, as Its members appear in animals, plants and yeast. Alignment of all known HMG boxes defined an unusually loose consensus sequence. We constructed phylogenetlc trees connecting the members of the HMG box superfamily in order to understand their evolution. This analysis led us to distinguish two subfamilies: one comprising proteins with a single sequence-specific HMG box, the other encompassing relatively non sequence-specific DNA-bindlng proteins with multiple HMG boxes. By studying the extent of diversification of the superfamily, we found that the speed of evolution was very different within the various groups of HMG-box containing factors. Comparison of the evolution of the two boxes of ABF2 and of mtTF1 implied different diversification models for these two proteins. Finally, we provide a tree for the highly complex group of SRY-like (‘Sox’ genes), clustering at least 40 different loci that rapidly diverged in various animal lineages.

Alteration in cell surface carbohydrates, and in particular cell surface sialylation, have been known to occur during oncogenic transformation. To examine the basis for such changes, we have transformed the rat fibroblast cell line FR3T3 with the oncogenes c-Ha-ras EJ, v-mycOK10, v-src, polyoma virus middle T or the transforming bovine papilloma virus 1 (BPV1), and measured the sialyltransferase activities of cellular lysates. We found that, in contrast to all other oncogenes examined, c-Ha-ras induced a striking increase in β-galactoside α-2,6-sialyltransferase (Gal α-2,6-ST) activity in FR3T3 cells. This increase in Gal α-2,6-ST activity resulted in the increased expression of cell surface α-2,6-linked sialic acid on cell surface glyco-conjugates, as determined by cell staining with fluoresceinlabelled Sambucus nigra agglutinin. Immunoprecipitation and immunofluorescence experiments revealed that the increase in Gal α-2,6-ST activity was due to an elevation of expression of the enzyme. Moreover, Northern analysis suggested that the increased expression of this enzyme was the result of an increase in the steady-state mRNA level of the Gal α-2,6-ST gene. These results support the notion that alterations seen in cell surface glycoconjugates during oncogenic transformation can be the result of altered expression of glycosyltransferases.