Evelyn C. Ilg

Clustered organization of S100 genes in human and mouse

S100 Ca2+-binding proteins became of major interest because of their differential expression in tissues and their association with human diseases. Earlier studies showed that 13 S100 genes are located as a cluster on human chromosome 1q21. Since a number of mouse S 100 genes, such as S100A4 and S100A6, have been localized to a syntenic region on mouse chromosome 3, we investigated if the S100 gene cluster exists in mouse and is structurally conserved during evolution. First we identified the cDNA sequences of mouse S100A1, S100A3 and S100A5. Then we isolated a 490 kb mouse YAC clone which gives a specific signal by FISH most likely on chromosome 3. Hybridization studies with different mouse S100 cDNAs revealed that eight mouse S100 genes are arranged in a clustered organization similar to that in human. The linkage relationships between the genes S100A8-S100A9 and S100A3-S100A4-S100A5-S100A6 were conserved during divergence of human and mouse about 70 million years ago. However, the separation of the mouse S100 genes S100A1 and S100A13 in comparison to the human linkage group suggests rearrangement processes between human and mouse. Our data demonstrate that the S100 gene cluster is structurally conserved during evolution. Further studies on the genomic organization of the S100 genes including various species could generate new insights into gene regulatory processes and phylogenetic relationships.

Localization of Ca2+-binding S100 proteins in epithelial tumours of the skin

Abstract The Ca2+-binding proteins S100A1, S100A2, S100A4, S100A6 and S100B were evaluated immunohistochemically in normal skin and skin appendage tumours. Epidermal basal cells, epithelial cells of sebaceous glands, hair follicle sheet epithelia and eccrine duct reacted strongly with an antiserum against human S100A2 but were nonreactive or weakly reactive to S100A1, S100A4, S100A6 and S100B. Varying types of skin appendage tumours and most peripheral cells in tumour nests of basal cell carcinoma and squamous cell carcinoma showed positive S100A2 immunoreactivity in neoplastic cells corresponding to basal cells but were nonreactive or faintly reactive for other S100 proteins. Langerhan’s cells and melanocytes were labelled by S100B. Basophilic cells of calcifying epithelioma were occasionally stained with S100A2 antiserum. Eccrine poroma did not react with any S100 antiserum. Mixed tumours of the skin containing neoplastic myoepithelial cells stained strongly for S100A2 and S100B but only faintly for S100A1, S100A4, S100A6. This is the first report on selective evaluation of different S100 proteins in normal skin. These antibodies are valuable tools for better characterization of skin appendage tumours.

Distribution of a specific calcium-binding protein of the S100 protein family, S100A6 (calcyclin), in subpopulations of neurons and glial cells of the adult rat nervous system

S100A6 (calcyclin) is a member of the large S100 Ca2+‐binding protein family, considered to activate several processes along the calcium signal transduction pathway including the regulation of cell growth, proliferation, secretion, and exocytosis. In the present study, the distribution of S100A6 in the rat nervous system was examined by immunohistochemistry with a goat antiserum against recombinant human S100A6, which recognizes the rat S100A6 homologue. The main S100A6‐immunoreactive elements were 1) neuronal somata and dendrites in some specific regions of the limbic system (e.g., the basolateral amygdaloid nucleus, ventral tip of the CA1‐subicular border region, entorhinal cortex, and parasubiculum), most of which were identified as a subpopulation of pyramidal cells; 2) olfactory receptor cells and olfactory nerve fibers and terminals in the olfactory bulb; 3) some tracts of the hindbrain and spinal cord (e.g., the spinal trigeminal tract, solitary tract, dorsal root fibers, and the tract of Lissauer) and their terminals (e.g., the principal sensory trigeminal nucleus, spinal trigeminal nucleus, nucleus of the solitary tract, marginal zone, substantia gelatinosa, and proper sensory nucleus of the dorsal horn), as well as some sensory neurons of their origins in the dorsal root and trigeminal ganglia; 4) a subpopulation of astrocytes in the white matter (e.g., the corpus callosum, cingulum, external capsule, internal capsule, and fimbria of the hippocampus) and around the ventricles; 5) some ependymal cells, especially around the central canal; and 6) Schwann cells. These results will improve our understanding of the diverse function of Ca2+‐binding proteins in the CNS. J. Comp. Neurol. 404:235–257, 1999.

Selective association of S100A6 (calcyclin)-immunoreactive astrocytes with the tangential migration pathway of subventricular zone cells in the rat

In adult rodents, proliferating cells in the subventricular zone of lateral ventricle tangentially migrate into the olfactory bulb, where they become the interneurons. The present immunocytochemical analysis revealed that S100A6 (calcyclin), a specific calcium-binding protein of the S100 family, is restrictedly distributed in some astrocytes in the tangential migration pathway of the rat. These results suggest that a particular type of astrocytes containing S100A6 is associated with the tangential migration pathway.

Immunohistochemical localization of S100A1 and S100A6 in postnatally developing salivary glands of rats

Abstract S100 proteins are calcium-binding proteins of the EF-hand superfamily and are involved in the regulation of a number of cellular processes. The present study deals with the immunohistochemical expression of S100A1 and S100A6 in the rat submandibular and sublingual glands during postnatal development from day 0 to 12 weeks. Expression of S100A1 was particularly concentrated in pillar and transition cells in the granular convoluted tubule (GCT) and in striated duct cells of the submandibular gland age 4 weeks to maturity. None or only weak staining for S100A1 was observed in the duct segment at 0–5 days. On the contrary, immunostaining of S100A6 was present in proacinar cells in undifferentiated submandibular gland at age 3 days to 2 weeks. S100A6 immunoreactivity in rat submandibular gland coexisted with chromogranin reactivity. It is possible that S100A6 regulates secretion of chromogranin in proacinar cells. Secretion of growth factors and biologically active peptides in the GCT are regulated by calcium signals, and S100A1 may be involved in the secretory mechanism of granular cells. S100A1 and S100A6 are potentially of great importance in secretory functions of granular cells and proacinar cells, as well as in rat salivary glands.