title: Temporal coherency between receptor expression, neural activity and AP-1-dependent transcription regulates Drosophila motoneuron dendrite development.
abstract: Neural activity has profound effects on the development of dendritic structure. Mechanisms that link neural activity to nuclear gene expression include activity-regulated factors, such as CREB, Crest or Mef2, as well as activity-regulated immediate-early genes, such as fos and jun. This study investigates the role of the transcriptional regulator AP-1, a Fos-Jun heterodimer, in activity-dependent dendritic structure development. We combine genetic manipulation, imaging and quantitative dendritic architecture analysis in a Drosophila single neuron model, the individually identified motoneuron MN5. First, Dα7 nicotinic acetylcholine receptors (nAChRs) and AP-1 are required for normal MN5 dendritic growth. Second, AP-1 functions downstream of activity during MN5 dendritic growth. Third, using a newly engineered AP-1 reporter we demonstrate that AP-1 transcriptional activity is downstream of Dα7 nAChRs and Calcium/calmodulin-dependent protein kinase II (CaMKII) signaling. Fourth, AP-1 can have opposite effects on dendritic development, depending on the timing of activation. Enhancing excitability or AP-1 activity after MN5 cholinergic synapses and primary dendrites have formed causes dendritic branching, whereas premature AP-1 expression or induced activity prior to excitatory synapse formation disrupts dendritic growth. Finally, AP-1 transcriptional activity and dendritic growth are affected by MN5 firing only during development but not in the adult. Our results highlight the importance of timing in the growth and plasticity of neuronal dendrites by defining a developmental period of activity-dependent AP-1 induction that is temporally locked to cholinergic synapse formation and dendritic refinement, thus significantly refining prior models derived from chronic expression studies.
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA. fernando.vonhoff@yale.edu
authors.forename: Fernando
authors.initials: F
authors.lastname: Vonhoff
authors.forename: Claudia
authors.initials: C
authors.lastname: Kuehn
authors.forename: Sonja
authors.initials: S
authors.lastname: Blumenstock
authors.forename: Subhabrata
authors.initials: S
authors.lastname: Sanyal
authors.forename: Carsten
authors.initials: C
authors.lastname: Duch
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D059329:Cholinergic Neurons / Q000378:metabolism; D003712:Dendrites / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D004789:Enzyme Activation; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D007150:Immunohistochemistry / Q000379:methods; D018613:Microscopy, Confocal / Q000379:methods; D008856:Microscopy, Fluorescence; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D009435:Synaptic Transmission; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D029721:Drosophila Proteins; D011978:Receptors, Nicotinic; D018808:Transcription Factor AP-1; C435749:kay protein, Drosophila; C113681:nicotinic acetylcholine receptor alpha-subunits, Drosophila; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2