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Neuron-glia interactions and glial enzyme expression in the mouse cerebellum
SYMPOSIUZ 2
Introduction to the Symposium on "The Role of Cell-Cell Interactions in Neurodifferentiation". Moscona, A. A., University of Chicago, Cummings Life Science Center, Chicago, Illinois, USA. Realization of genetic programs for morphogenesis and differentiation in nervous systems requires conditions and signals resulting largely from cell interactions. Many of these depend on surface-contacts between homotypic or heterotypic cells; others involve cell reactions with extracellular matrix materials (ECM), or with hormones and trophic factors; still others require both cell contact and environmental signals. As the full scope of these processes comes to light, the concept of communication in neural development is acquiring new content and significance. Interest increasingly is drawn to the detailed molecular and ultrastructural basis of these interactions in histological patterning of cells and phenotypic expression. Studies on glia cells are revealing new aspects of their partnership with neurons. Studies on ECM aim to unravel the formation of these cell products and how they, in turn, modulate cell properties and behavior. In all of this, the unifying theme is the cell surface, because of its strategic role in environmental surveillance, morphogenetic cell-cell recognition, intercellular communication, regulation of cell growth, and gene expression. The papers in this symposium are thematically linked by this central concept. They discuss the significance of cell interactions in neurodevelopment and spotlight new directions of research in this area.
Neuron-glia interactions and g l i a l enzyme expression in the mouse cerebellum Fisher, M. University of Utah School of Medicine, Department of Anatomy, Salt Lake City, Utah 84132, U.S.A. There are several mouse neurological mutants that have reduced cerebellar levels of the developmentally regulated enzyme, glycerol-3-phosphate dehydrogenase (GPDH). The low levels of enzyme a c t i v i t y in these mutants correlate with reduced intensity of immunohistochemically demonstrable enzyme in the Bergmann glia perikarya and the molecular layer. The affected mutants suffer from numerous documented cytological defects. All of these mutants have in common a Purkinje cell defect that varies in severity among the mutant genotypes, I t is hypothesized that maintenance of the high level of GPDH a c t i v i t y seen normally in Bergmann glia is dependent upon the early and sustained interaction between Bergmann glia and their neighboring Purkinje cells. Immunohistochemical studies of GPDHexpression in Purkinje cell deficient cerebella from the mutants Lurcher, nervous and Purkinje cell degeneration, and from LgJ+ +~ +/+ and ~d/p_G~ ~ +/+ chimeric mice support this hypothesis. In each of these cases GPDH-positive Bergmann glia are found only when there is a normal Purkinje cell nearb~ although Bergmann glia can be shown to be present throughout the cerebellar cortex by immunostaining with antiserum against the g l i a l f i b r i l l a r y acidic protein. The influence of neuronal-glial interactions on glia-specific gene expression in embryonic retina. By Linser, P. J., C. V. Whitney Laboratory of the Univ. of Florida, St. Augustine, Florida, and Moscona, A.A., Cummings Life Science Center, Univ. of Chicago,Chicago,Ill. We have shown that the enzymes glutamine synthetase (GS) and carbonic anhydrase-C (CA-C) are specifically compartmentalized in the M~ller glia cells of the mature chicken neural retina. Both GS and CA-C are developmentally regulated in embryonic retina and show striking and different patterns of expression during retina ontogeny. GS begins to rise sharply late in development during functional maturation of the retina. CA-C also is expressed suddenly, but at a much earlier stage. Using these enzymes as biochemical and immunohistochemical markers, we have studied the cytodifferentiation of retina glia in relation to the influence of tissue architecture and cell-cell interactions. Single cell suspensions of dissociated embryonic retinae were used to generate tissue-like cellular aggregates, adherent "monolayer" cultures containing both neurons and glia, and monoSayer cultures of either neurons or glia. Immunohistochemical examination of marker expression showed that the cortisol-induced accumulation of high GS levels in M~ller glia cells is dependent on neuronal-glial juxtapositioning and probably direct cell contact. CA-C expression in M~ller cells is regulated independently of those hormonal and heterotypic cell interactions that are critical to GS expression. These observations will be discussed in relation to the different roles of these enzymes in retina function.
Introduction to the Symposium on "The Role of Cell-Cell Interactions in Neurodifferentiation". Moscona, A. A., University of Chicago, Cummings Life Science Center, Chicago, Illinois, USA. Realization of genetic programs for morphogenesis and differentiation in nervous systems requires conditions and signals resulting largely from cell interactions. Many of these depend on surface-contacts between homotypic or heterotypic cells; others involve cell reactions with extracellular matrix materials (ECM), or with hormones and trophic factors; still others require both cell contact and environmental signals. As the full scope of these processes comes to light, the concept of communication in neural development is acquiring new content and significance. Interest increasingly is drawn to the detailed molecular and ultrastructural basis of these interactions in histological patterning of cells and phenotypic expression. Studies on glia cells are revealing new aspects of their partnership with neurons. Studies on ECM aim to unravel the formation of these cell products and how they, in turn, modulate cell properties and behavior. In all of this, the unifying theme is the cell surface, because of its strategic role in environmental surveillance, morphogenetic cell-cell recognition, intercellular communication, regulation of cell growth, and gene expression. The papers in this symposium are thematically linked by this central concept. They discuss the significance of cell interactions in neurodevelopment and spotlight new directions of research in this area.
Neuron-glia interactions and g l i a l enzyme expression in the mouse cerebellum Fisher, M. University of Utah School of Medicine, Department of Anatomy, Salt Lake City, Utah 84132, U.S.A. There are several mouse neurological mutants that have reduced cerebellar levels of the developmentally regulated enzyme, glycerol-3-phosphate dehydrogenase (GPDH). The low levels of enzyme a c t i v i t y in these mutants correlate with reduced intensity of immunohistochemically demonstrable enzyme in the Bergmann glia perikarya and the molecular layer. The affected mutants suffer from numerous documented cytological defects. All of these mutants have in common a Purkinje cell defect that varies in severity among the mutant genotypes, I t is hypothesized that maintenance of the high level of GPDH a c t i v i t y seen normally in Bergmann glia is dependent upon the early and sustained interaction between Bergmann glia and their neighboring Purkinje cells. Immunohistochemical studies of GPDHexpression in Purkinje cell deficient cerebella from the mutants Lurcher, nervous and Purkinje cell degeneration, and from LgJ+ +~ +/+ and ~d/p_G~ ~ +/+ chimeric mice support this hypothesis. In each of these cases GPDH-positive Bergmann glia are found only when there is a normal Purkinje cell nearb~ although Bergmann glia can be shown to be present throughout the cerebellar cortex by immunostaining with antiserum against the g l i a l f i b r i l l a r y acidic protein. The influence of neuronal-glial interactions on glia-specific gene expression in embryonic retina. By Linser, P. J., C. V. Whitney Laboratory of the Univ. of Florida, St. Augustine, Florida, and Moscona, A.A., Cummings Life Science Center, Univ. of Chicago,Chicago,Ill. We have shown that the enzymes glutamine synthetase (GS) and carbonic anhydrase-C (CA-C) are specifically compartmentalized in the M~ller glia cells of the mature chicken neural retina. Both GS and CA-C are developmentally regulated in embryonic retina and show striking and different patterns of expression during retina ontogeny. GS begins to rise sharply late in development during functional maturation of the retina. CA-C also is expressed suddenly, but at a much earlier stage. Using these enzymes as biochemical and immunohistochemical markers, we have studied the cytodifferentiation of retina glia in relation to the influence of tissue architecture and cell-cell interactions. Single cell suspensions of dissociated embryonic retinae were used to generate tissue-like cellular aggregates, adherent "monolayer" cultures containing both neurons and glia, and monoSayer cultures of either neurons or glia. Immunohistochemical examination of marker expression showed that the cortisol-induced accumulation of high GS levels in M~ller glia cells is dependent on neuronal-glial juxtapositioning and probably direct cell contact. CA-C expression in M~ller cells is regulated independently of those hormonal and heterotypic cell interactions that are critical to GS expression. These observations will be discussed in relation to the different roles of these enzymes in retina function.