A novel role of the glial fate determinant glial cells missing in hematopoiesis.
Glial cell deficient/Glial cells missing (Glide/Gcm) transcription factor is expressed in all glial precursors of the Drosophila embryo. Gcm is necessary and sufficient to induce glial differentiation but also plays a role in other cell types, by interacting with specific factors. To find potential partners of Gcm which trigger these other pathways, we performed a yeast two-hybrid screen and identified dpias, a gene involved in post-embryonic hematopoiesis. dpias larvae show melanotic tumors due to excess of lamellocytes, a hemocyte lineage that is involved in non-self recognition. We here show that blocking Gcm activity also triggers melanotic tumors and that gcm interacts genetically with dpias. Moreover, the members of the Janus Kinase (JAK)/ Signal Transducer and Activator of Transcription (STAT) pathway, which are known for their role in the vertebrate and invertebrate immune system and are required for dpias-dependent tumor formation, act downstream of Gcm. Altogether, this study identifies an unpredicted role of Gcm, dictated by its cofactor dpias, allowing Gcm to act in a specific pathway. Together with the recent finding that glia act as scavengers during development and in pathological conditions, our data open new perspectives onto the cellular and molecular pathways involved in non-self recognition within and outside the nervous system.
Jacques
Cécile
C
Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/ULP, C.U. de Strasbourg, France.
Soustelle
Laurent
L
Nagy
István
I
Diebold
Céline
C
Giangrande
Angela
A
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D007814:Larva / Q000254:growth & development / Q000378:metabolism; D008546:Melanoma, Experimental / Q000209:etiology / Q000235:genetics / Q000473:pathology; D008954:Models, Biological; D009154:Mutation; D009457:Neuroglia / Q000166:cytology*; D010641:Phenotype; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014018:Tissue Distribution; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D017931:DNA Primers; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C102805:GCM protein, Drosophila; D050828:Protein Inhibitors of Activated STAT; D014157:Transcription Factors