Genomes & Developmental Control Expression profiling of glial genes during Drosophila embryogenesis (original) (raw)
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Expression profiling of glial genes during Drosophila embryogenesis
Developmental Biology, 2006
In the central nervous system of Drosophila, the induction of the glial cell fate is dependent on the transcription factor glial cells missing (gcm). Though a considerable number of other genes have been shown to be expressed in all or in subsets of glial cells, the course of glial cell differentiation and subtype specification is only poorly understood. This prompted us to design a whole genome microarray approach comparing gcm gain-of-function and, for the first time, gcm loss-of-function genetics to wildtype in time course experiments along embryogenesis. The microarray data were analyzed with special emphasis on the temporal profile of differential regulation. A comparison of both experiments enabled us to identify more than 300 potential gcm target genes. Validation by in situ hybridization revealed expression in glial cells, macrophages, and tendon cells (all three cell types depend on gcm) for 70 genes, of which more than 50 had been unknown to be under gcm control. Eighteen genes are exclusively expressed in glial cells, and their dependence on gcm was confirmed in situ. Initial considerations regarding the role of the newly discovered glial genes are discussed based on gene ontology and the temporal profile and subtype specificity of their expression. This collection of glial genes provides an important basis for the clarification of the genetic network controlling various aspects of glial development and function.
Development, 2003
embryonic brain. However, cultures from mouse Gcm1deficient mouse brains did not exhibit significant reductions in the number of astrocytes. Furthermore, in situ hybridization analysis of mouse Gcm1 mRNA revealed distinct patterns of expression in comparison with other well-known glial markers. The mammalian homolog of Drosophila gcm, mouse Gcm1, exhibits the potential to induce gliogenesis, but may function in the generation of a minor subpopulation of glial cells.
Glial cells missing: A binary switch between neuronal and glial determination in drosophila
Cell, 1995
In the Drosophila CNS, both neurons and glia are derived from neuroblasts. We have identified a gene, glial cells missing (gcm), that encodes a novel nuclear protein expressed transiently in early glial cells. Its mutation causes presumptive glial cells to differentiate into neurons, whereas its ectopic expression forces virtually all CNS cells to become glial cells. Thus, gcm functions as a binary switch that turns on glial fate while inhibiting default neuronal fate of the neuroblasts and their progeny. Similar results are also obtained in the PNS. Analyses of the mutant revealed that "pioneer neurons" can find correct pathways without glial cells and that neurons and glia have a common molecular basis for individual identity.
Glial cell development in Drosophila
International Journal of Developmental Neuroscience, 2001
In the Drosophila central nervous system (CNS) about 10% of the cells are of glial nature. A set of molecular markers has allowed unraveling a number of genes controlling glial cell fate determination as well as genes required for glial cell differentiation.
Development, 1997
Two classes of glial cells are found in the embryonic Drosophila CNS, midline glial cells and lateral glial cells. Midline glial development is triggered by EGF-receptor signalling, whereas lateral glial development is controlled by the gcm gene. Subsequent glial cell differentiation depends partly on the pointed gene. Here we describe a novel component required for all CNS glia development. The tramtrack gene encodes two zinc-finger proteins, one of which, ttkp69, is expressed in all non-neuronal CNS cells. We show that ttkp69 is downstream of gcm and can repress neuronal differentiation. Double mutant analysis and coexpression experiments indicate that glial cell differentiation may depend on a dual process, requiring the activation of glial differentiation by pointed and the concomitant repression of neuronal development by tramtrack.
Neuron, 2005
To determine the relationship between gcm gene expression and the developmental sequence leading to glial fate commitment, we conducted lineage analysis experiments of epithelial and marginal glial cells using MARCM. The MARCM stock w hs-FLP tubP-Gal80 FRT19A; UAS-nlacZ UAS-cd8GFP; tubP-Gal4/Tm6b (kindly provided by A. Gould; Bello et al., 2003) was crossed to a wild type FRT19A line. Mitotic recombination was induced by heat shocking larvae in a 37°C water bath for 70 minutes at 48 hours after egg laying. Animals were analyzed during the late third instar larval stage. To score the composition of clones, glial cells and neurons were visualized using antibodies against the differentiation markers Repo and Elav, respectively. From 98 clones (corresponding to 92 optic lobes), images were taken at different focal planes throughout the optic lobe and some of these were processed to obtain a 3D view.
Transcriptional regulation of glial cell specification
Developmental Biology, 2003
Neuronal differentiation relies on proneural factors that also integrate positional information and contribute to the specification of the neuronal type. The molecular pathway triggering glial specification is not understood yet. In Drosophila, all lateral glial precursors and glial-promoting activity have been identified, which provides us with a unique opportunity to dissect the regulatory pathways controlling glial differentiation and specification. Although glial lineages are very heterogeneous with respect to position, time of differentiation, and lineage tree, they all express and require two homologous genes, glial cell deficient/glial cell missing (glide/gcm) and glide2, that act in concert, with glide/gcm constituting the major glial-promoting factor . Here, we show that glial specification resides in glide/gcm transcriptional regulation. The glide/gcm promoter contains lineage-specific elements as well as quantitative and turmoil elements scattered throughout several kilobases. Interestingly, there is no correlation between a specific regulatory element and the type of glial lineage. Thus, the glial-promoting factor acts as a naive switch-on button that triggers gliogenesis in response to multiple pathways converging onto its promoter. Both negative and positive regulation are required to control glide/gcm expression, indicating that gliogenesis is actively repressed in some neural lineages.
Mechanisms of Development, 2008
Cell lineage Longitudinal glia Castor Drosophila A B S T R A C T In the Drosophila embryonic CNS several subtypes of glial cells develop, which arrange themselves at characteristic positions and presumably fulfil specific functions. The mechanisms leading to the specification and differentiation of glial subtypes are largely unknown. By DiI labelling in glia-specific Gal4 lines we have clarified the lineages of the lateral glia in the embryonic ventral nerve cord and linked each glial cell to a specific stem cell. For the lineage of the longitudinal glioblast we show that it consists of 9 cells, which acquire at least four different identities. A large collection of molecular markers (many of them representing transcription factors and potential Gcm target genes) reveals that individual glial cells express specific combinations of markers. However, cluster analysis uncovers similar combinatorial codes for cells within, and significant differences between the categories of surface-associated, cortex-associated, and longitudinal glia. Glial cells derived from the same stem cell may be homogeneous (though not identical; stem cells NB1-1, NB5-6, NB6-4, LGB) or heterogeneous (NB7-4, NB1-3) with regard to gene expression. In addition to providing a powerful tool to analyse the fate of individual glial cells in different genetic backgrounds, each of these marker genes represents a candidate factor involved in glial specification or differentiation. We demonstrate this by the analysis of a castor loss of function mutation, which affects the number and migration of specific glial cells. (G.M. Technau). M E C H A N I S M S O F D E V E L O P M E N T 1 2 5 ( 2 0 0 8 ) 5 4 2 -5 5 7 a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / m o d o
Alteration of cell fate by ectopic expression of Drosophila glial cells missing in non-neural cells
Development Genes and Evolution, 1998
The glial cells missing (gcm) gene encodes an essential transcription factor that converts neuronal precursor cells to glial fate in the Drosophila nervous system. In this study, we tested effects of gcm ectopic expression on fate of non-neural cells. When gcm expression was continuously induced in epidermal cells from around stage 9, these cells started to exhibit mesenchymal cell morphology at stage 13, which was preceded by the onset of expression of Repo, a glial marker. The morphological change was coincident with loss of expression of an epidermal cell-adhesion molecule. In addition to the epidermis, fate of mesodermal cells was also affected by gcm ectopic expression. These findings suggest that gcm can convert gene expression and cell morphology even outside the neuroectoderm.