title: Double-bromo and extraterminal (BET) domain proteins regulate dendrite morphology and mechanosensory function.
abstract: A complex array of genetic factors regulates neuronal dendrite morphology. Epigenetic regulation of gene expression represents a plausible mechanism to control pathways responsible for specific dendritic arbor shapes. By studying the Drosophila dendritic arborization (da) neurons, we discovered a role of the double-bromodomain and extraterminal (BET) family proteins in regulating dendrite arbor complexity. A loss-of-function mutation in the single Drosophila BET protein encoded by female sterile 1 homeotic [fs(1)h] causes loss of fine, terminal dendritic branches. Moreover, fs(1)h is necessary for the induction of branching caused by a previously identified transcription factor, Cut (Ct), which regulates subtype-specific dendrite morphology. Finally, disrupting fs(1)h function impairs the mechanosensory response of class III da sensory neurons without compromising the expression of the ion channel NompC, which mediates the mechanosensitive response. Thus, our results identify a novel role for BET family proteins in regulating dendrite morphology and a possible separation of developmental pathways specifying neural cell morphology and ion channel expression. Since the BET proteins are known to bind acetylated histone tails, these results also suggest a role of epigenetic histone modifications and the "histone code," in regulating dendrite morphology.
authors.affiliation: Neuroscience Graduate Program, University of California at San Francisco, San Francisco, California 94158, USA; Howard Hughes Medical Institute, Department of Physiology, Department of Biochemistry and Biophysics, University of California at San Francisco at San Francisco, California 94158, USA.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Bagley
authors.affiliation: Howard Hughes Medical Institute, Department of Physiology, Department of Biochemistry and Biophysics, University of California at San Francisco at San Francisco, California 94158, USA.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Howard Hughes Medical Institute, Department of Physiology, Department of Biochemistry and Biophysics, University of California at San Francisco at San Francisco, California 94158, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Howard Hughes Medical Institute, Department of Physiology, Department of Biochemistry and Biophysics, University of California at San Francisco at San Francisco, California 94158, USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Wildonger
authors.affiliation: Howard Hughes Medical Institute, Department of Physiology, Department of Biochemistry and Biophysics, University of California at San Francisco at San Francisco, California 94158, USA yuhnung.jan@ucsf.edu.
authors.forename: Lily Yeh
authors.initials: LY
authors.lastname: Jan
authors.affiliation: Howard Hughes Medical Institute, Department of Physiology, Department of Biochemistry and Biophysics, University of California at San Francisco at San Francisco, California 94158, USA yuhnung.jan@ucsf.edu.
authors.forename: Yuh Nung
authors.initials: YN
authors.lastname: Jan
mesh_terms: D000818:Animals; D003712:Dendrites / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011984:Sensory Receptor Cells / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C066381:ct protein, Drosophila; C109569:fs(1)h protein, Drosophila
keywords: dendrite morphogenesis; double bromodomain and extraterminal; epigenetics; female sterile 1 homeotic; histone acetylation; mechanosensory function