title: The Drosophila transcription factor Adf-1 (nalyot) regulates dendrite growth by controlling FasII and Staufen expression downstream of CaMKII and neural activity.
abstract: Memory deficits in Drosophila nalyot mutants suggest that the Myb family transcription factor Adf-1 is an important regulator of developmental plasticity in the brain. However, the cellular functions for this transcription factor in neurons or molecular mechanisms by which it regulates plasticity remain unknown. Here, we use in vivo 3D reconstruction of identifiable larval motor neuron dendrites to show that Adf-1 is required cell autonomously for dendritic development and activity-dependent plasticity of motor neurons downstream of CaMKII. Adf-1 inhibition reduces dendrite growth and neuronal excitability, and results in motor deficits and altered transcriptional profiles. Surprisingly, analysis by comparative chromatin immunoprecipitation followed by sequencing (ChIP-Seq) of Adf-1, RNA Polymerase II (Pol II), and histone modifications in Kc cells shows that Adf-1 binding correlates positively with high Pol II-pausing indices and negatively with active chromatin marks such as H3K4me3 and H3K27ac. Consistently, the expression of Adf-1 targets Staufen and Fasciclin II (FasII), identified through larval brain ChIP-Seq for Adf-1, is negatively regulated by Adf-1, and manipulations of these genes predictably modify dendrite growth. Our results imply mechanistic interactions between transcriptional and local translational machinery in neurons as well as conserved neuronal growth mechanisms mediated by cell adhesion molecules, and suggest that CaMKII, Adf-1, FasII, and Staufen influence crucial aspects of dendrite development and plasticity with potential implications for memory formation. Further, our experiments reveal molecular details underlying transcriptional regulation by Adf-1, and indicate active interaction between Adf-1 and epigenetic regulators of gene expression during activity-dependent neuronal plasticity.
authors.affiliation: Department of Cell Biology, School of Medicine, and Department of Biology, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Timmerman
authors.forename: Somu
authors.initials: S
authors.lastname: Suppiah
authors.forename: Baraka V
authors.initials: BV
authors.lastname: Gurudatta
authors.forename: Jingping
authors.initials: J
authors.lastname: Yang
authors.forename: Christopher
authors.initials: C
authors.lastname: Banerjee
authors.forename: David J
authors.initials: DJ
authors.lastname: Sandstrom
authors.forename: Victor G
authors.initials: VG
authors.lastname: Corces
authors.forename: Subhabrata
authors.initials: S
authors.lastname: Sanyal
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D007814:Larva / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C072263:Adf1 protein, Drosophila; D015816:Cell Adhesion Molecules, Neuronal; D029721:Drosophila Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C051642:fasciclin II; C069927:stau protein, Drosophila; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2