RESUMO
In the nervous system, glial cells need to be specified from a set of progenitor cells. In the developing Drosophila eye, perineurial glia proliferate and differentiate as wrapping glia in response to a neuronal signal conveyed by the FGF receptor pathway. To unravel the underlying transcriptional network we silenced all genes encoding predicted DNA-binding proteins in glial cells using RNAi. Dref and other factors of the TATA box-binding protein-related factor 2 (TRF2) complex were previously predicted to be involved in cellular metabolism and cell growth. Silencing of these genes impaired early glia proliferation and subsequent differentiation. Dref controls proliferation via activation of the Pdm3 transcription factor, whereas glial differentiation is regulated via Dref and the homeodomain protein Cut. Cut expression is controlled independently of Dref by FGF receptor activity. Loss- and gain-of-function studies show that Cut is required for glial differentiation and is sufficient to instruct the formation of membrane protrusions, a hallmark of wrapping glial morphology. Our work discloses a network of transcriptional regulators controlling the progression of a naïve perineurial glia towards the fully differentiated wrapping glia.
Assuntos
Drosophila melanogaster/embriologia , Olho/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Células-Tronco Neurais/citologia , Neurogênese/genética , Neuroglia/citologia , Animais , Proliferação de Células/genética , Proteínas de Ligação a DNA/genética , Proteínas de Drosophila/biossíntese , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Ativação Enzimática , Olho/inervação , Redes Reguladoras de Genes , Proteínas de Homeodomínio/biossíntese , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Proteínas Nucleares/biossíntese , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fatores do Domínio POU/genética , Fatores do Domínio POU/metabolismo , Interferência de RNA , RNA Interferente Pequeno , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Proteína 2 de Ligação a Repetições Teloméricas/genética , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transdução GenéticaRESUMO
The development of multicellular organisms requires the well balanced and coordinated migration of many cell types. This is of particular importance within the developing nervous system, where glial cells often move long distances to reach their targets. The majority of glial cells in the peripheral nervous system of the Drosophila embryo is derived from the CNS and migrates along motor axons toward their targets. In the developing Drosophila eye, CNS-derived glial cells move outward toward the nascent photoreceptor cells, but the molecular mechanisms coupling the migration of glial cells with the growth of the eye imaginal disc are mostly unknown. Here, we used an enhancer trap approach to identify the gene spinster, which encodes a multipass transmembrane protein involved in endosome-lysosome trafficking, as being expressed in many glial cells. spinster mutants are characterized by glial overmigration. Genetic experiments demonstrate that Spinster modulates the activity of several signaling cascades. Within the migrating perineurial glial cells, Spinster is required to downregulate Dpp (Decapentaplegic) signaling activity, which ceases migratory abilities. In addition, Spinster affects the growth of the carpet cell, which indirectly modulates glial migration.
