title: Interlocked loops trigger lineage specification and stable fates in the Drosophila nervous system.
abstract: 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.
authors: 1] Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404 Illkirch, France [2] Centre National de la Recherche Scientifique, UMR7104, 67404 Illkirch, France [3] Institut National de la Santé et de la Recherche Médicale, U964, 67404 Illkirch, France [4] Université de Strasbourg, 67404 Illkirch, France [5] [6].
authors: Hakima
authors: H
authors: Flici
authors: 1] Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404 Illkirch, France [2] Centre National de la Recherche Scientifique, UMR7104, 67404 Illkirch, France [3] Institut National de la Santé et de la Recherche Médicale, U964, 67404 Illkirch, France [4] Université de Strasbourg, 67404 Illkirch, France [5].
authors: Pierre B
authors: PB
authors: Cattenoz
authors: 1] Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404 Illkirch, France [2] Centre National de la Recherche Scientifique, UMR7104, 67404 Illkirch, France [3] Institut National de la Santé et de la Recherche Médicale, U964, 67404 Illkirch, France [4] Université de Strasbourg, 67404 Illkirch, France.
authors: Orban
authors: O
authors: Komonyi
authors: 1] Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404 Illkirch, France [2] Centre National de la Recherche Scientifique, UMR7104, 67404 Illkirch, France [3] Institut National de la Santé et de la Recherche Médicale, U964, 67404 Illkirch, France [4] Université de Strasbourg, 67404 Illkirch, France [5].
authors: Pietro
authors: P
authors: Laneve
authors: 1] Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404 Illkirch, France [2] Centre National de la Recherche Scientifique, UMR7104, 67404 Illkirch, France [3] Institut National de la Santé et de la Recherche Médicale, U964, 67404 Illkirch, France [4] Université de Strasbourg, 67404 Illkirch, France [5].
authors: Berra
authors: B
authors: Erkosar
authors: 1] Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404 Illkirch, France [2] Centre National de la Recherche Scientifique, UMR7104, 67404 Illkirch, France [3] Institut National de la Santé et de la Recherche Médicale, U964, 67404 Illkirch, France [4] Université de Strasbourg, 67404 Illkirch, France [5].
authors: Omer F
authors: OF
authors: Karatas
authors: Biozentrum University of Basel, Klingelbergstrasse 50/70CH, 4056 Basel, Switzerland.
authors: Heinrich
authors: H
authors: Reichert
authors: 1] Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404 Illkirch, France [2] Centre National de la Recherche Scientifique, UMR7104, 67404 Illkirch, France [3] Institut National de la Santé et de la Recherche Médicale, U964, 67404 Illkirch, France [4] Université de Strasbourg, 67404 Illkirch, France [5].
authors: Sara
authors: S
authors: Berzsenyi
authors: 1] Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404 Illkirch, France [2] Centre National de la Recherche Scientifique, UMR7104, 67404 Illkirch, France [3] Institut National de la Santé et de la Recherche Médicale, U964, 67404 Illkirch, France [4] Université de Strasbourg, 67404 Illkirch, France.
authors: Angela
authors: A
authors: Giangrande
mesh_terms: D000818:Animals; D019070:Cell Lineage; D004330:Drosophila / Q000166:cytology / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D009420:Nervous System / Q000166:cytology* / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D014157:Transcription Factors