title: Functional genomic analyses of two morphologically distinct classes of Drosophila sensory neurons: post-mitotic roles of transcription factors in dendritic patterning.
abstract: BACKGROUND
  Neurons are one of the most structurally and functionally diverse cell types found in nature, owing in large part to their unique class specific dendritic architectures. Dendrites, being highly specialized in receiving and processing neuronal signals, play a key role in the formation of functional neural circuits. Hence, in order to understand the emergence and assembly of a complex nervous system, it is critical to understand the molecular mechanisms that direct class specific dendritogenesis.
  
  
  RESULTS
  We have used the Drosophila dendritic arborization (da) neurons to gain systems-level insight into dendritogenesis by a comparative study of the morphologically distinct Class-I (C-I) and Class-IV (C-IV) da neurons. We have used a combination of cell-type specific transcriptional expression profiling coupled to a targeted and systematic in vivo RNAi functional validation screen. Our comparative transcriptomic analyses have revealed a large number of differentially enriched/depleted gene-sets between C-I and C-IV neurons, including a broad range of molecular factors and biological processes such as proteolytic and metabolic pathways. Further, using this data, we have identified and validated the role of 37 transcription factors in regulating class specific dendrite development using in vivo class-specific RNAi knockdowns followed by rigorous and quantitative neurometric analysis.
  
  
  CONCLUSIONS
  This study reports the first global gene-expression profiles from purified Drosophila C-I and C-IV da neurons. We also report the first large-scale semi-automated reconstruction of over 4,900 da neurons, which were used to quantitatively validate the RNAi screen phenotypes. Overall, these analyses shed global and unbiased novel insights into the molecular differences that underlie the morphological diversity of distinct neuronal cell-types. Furthermore, our class-specific gene expression datasets should prove a valuable community resource in guiding further investigations designed to explore the molecular mechanisms underlying class specific neuronal patterning.
authors: School of Systems Biology, Krasnow Institute for Advanced Study, George Mason University, Fairfax, Virginia, United States of America.
authors: Eswar Prasad R
authors: EP
authors: Iyer
authors: Srividya Chandramouli
authors: SC
authors: Iyer
authors: Luis
authors: L
authors: Sullivan
authors: Dennis
authors: D
authors: Wang
authors: Ramakrishna
authors: R
authors: Meduri
authors: Lacey L
authors: LL
authors: Graybeal
authors: Daniel N
authors: DN
authors: Cox
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D003712:Dendrites / Q000235:genetics*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D023281:Genomics / Q000379:methods*; D008938:Mitosis / Q000235:genetics*; D055495:Neurogenesis; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D034622:RNA Interference; D015203:Reproducibility of Results; D011984:Sensory Receptor Cells / Q000166:cytology* / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D059467:Transcriptome / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D014157:Transcription Factors
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