Fiche publication
Date publication
novembre 2015
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GIANGRANDE Angela
,
Dr CATTENOZ Pierre
Tous les auteurs :
Cattenoz PB, Popkova A, Southall T, Aiello G, Brand A, Giangrande A
Lien Pubmed
Résumé
High throughput screens allow us to understand how transcription factors trigger developmental processes including cell specification. A major challenge is the identification of their binding sites because feedback loops and homeostatic interactions may mask the direct impact of those factors in transcriptome analyses. Moreover, this approach dissects the downstream signaling cascades and facilitates the identification of conserved transcriptional programs. Here we show the results and the validation of a DamID genome-wide screen that identifies the direct targets of Glide/Gcm, a potent transcription factor that controls glia, hemocyte and tendon cell differentiation in Drosophila. The screen identifies many genes that had not been previously associated to Glide/Gcm and highlights three major signaling pathways interacting with Glide/Gcm: Notch, Hedgehog and JAK/STAT, which all involve feedback loops. Furthermore, the screen identifies effector molecules that are necessary for cell-cell interactions during late developmental processes and/or in ontogeny. Typically, Immunoglobulin domain-containing (or Ig-domain-containing) proteins control cell adhesion and axonal navigation (PATEL AND VAN VACTOR 2002). This shows that early and transiently expressed fate determinants not only control other transcription factors that in turn implement a specific developmental program but also directly affect late developmental events and cell function. Finally, while the mammalian genome contains two orthologous Gcm genes, their function has been demonstrated in vertebrate-specific tissues, placenta and parathyroid glands, begging questions on the evolutionary conservation of the Gcm cascade in higher organisms. Here we provide the first evidence for the conservation of Gcm direct targets in humans. In sum, this work uncovers novel aspects of cell-specification and sets the bases for further understanding of the role of conserved Gcm gene regulatory cascades.
Référence
Genetics. 2015 Nov 13. pii: genetics.115.182154.
