Polycomb group genes are required for neural stem cell survival in postembryonic neurogenesis of Drosophila.
Genes of the Polycomb group (PcG) are part of a cellular memory system that maintains appropriate inactive states of Hox gene expression in Drosophila. Here, we investigate the role of PcG genes in postembryonic development of the Drosophila CNS. We use mosaic-based MARCM techniques to analyze the role of these genes in the persistent larval neuroblasts and progeny of the central brain and thoracic ganglia. We find that proliferation in postembryonic neuroblast clones is dramatically reduced in the absence of Polycomb, Sex combs extra, Sex combs on midleg, Enhancer of zeste or Suppressor of zeste 12. The proliferation defects in these PcG mutants are due to the loss of neuroblasts by apoptosis in the mutant clones. Mutation of PcG genes in postembryonic lineages results in the ectopic expression of posterior Hox genes, and experimentally induced misexpression of posterior Hox genes, which in the wild type causes neuroblast death, mimics the PcG loss-of-function phenotype. Significantly, full restoration of wild-type-like properties in the PcG mutant lineages is achieved by blocking apoptosis in the neuroblast clones. These findings indicate that loss of PcG genes leads to aberrant derepression of posterior Hox gene expression in postembryonic neuroblasts, which causes neuroblast death and termination of proliferation in the mutant clones. Our findings demonstrate that PcG genes are essential for normal neuroblast survival in the postembryonic CNS of Drosophila. Moreover, together with data on mammalian PcG genes, they imply that repression of aberrant reactivation of Hox genes may be a general and evolutionarily conserved role for PcG genes in CNS development.
Bello
Bruno
B
Biozentrum, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland. Bruno.Bello@unibas.ch
Holbro
Niklaus
N
Reichert
Heinrich
H
D000818:Animals; D051943:Antennapedia Homeodomain Protein; D017209:Apoptosis / Q000235:genetics; D019070:Cell Lineage; D049109:Cell Proliferation; D002470:Cell Survival; D002490:Central Nervous System / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D004268:DNA-Binding Proteins; D004330:Drosophila / Q000166:cytology / Q000235:genetics / Q000254:growth & development*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D005801:Genes, Homeobox / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D009687:Nuclear Proteins; D063150:Polycomb Repressive Complex 1; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*
D051943:Antennapedia Homeodomain Protein; C497974:Antp protein, Drosophila; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; C066770:Pc protein, Drosophila; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; C099357:SCM protein, Drosophila; C083329:E(z) protein, Drosophila; D063151:Polycomb Repressive Complex 2; D063150:Polycomb Repressive Complex 1