Interlocked loops trigger lineage specification and stable fates in the Drosophila nervous system.
Fiche publication
Date publication
juillet 2014
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GIANGRANDE Angela, Dr CATTENOZ Pierre
Tous les auteurs :
Flici H, Cattenoz PB, Komonyi O, Laneve P, Erkosar B, Karatas OF, Reichert H, Berzsenyi S, Giangrande A
Lien Pubmed
Résumé
Multipotent precursors are plastic cells that generate different, stable fates at the correct number, place and time, to allow tissue and organ formation. While fate determinants are known to trigger specific transcriptional programs, the molecular pathway driving the progression from multipotent precursors towards stable and specific identities remains poorly understood. Here we demonstrate that, in Drosophila neural precursors, the glial determinant glial cell missing (Gcm) acts as a 'time bomb' and triggers its own degradation once the glial programme is stably activated. This requires a sequence of transcriptional and posttranscriptional loops, whereby a Gcm target first affects the expression and then acetylation of the fate determinant, thus controlling Gcm levels and stability over time. Defective homeostasis between the loops alters the neuron:glia ratio and freezes cells in an intermediate glial/neuronal phenotype. In sum, we identify an efficient strategy triggering cell identity, a process altered in pathological conditions such as cancer.
Mots clés
Animals, Cell Lineage, Drosophila, cytology, Drosophila Proteins, genetics, Gene Expression Regulation, Developmental, Nervous System, cytology, Neuroglia, cytology, Neurons, cytology, Transcription Factors, genetics
Référence
Nat Commun. 2014 Jul;5:4484