title: Turtle functions downstream of Cut in differentially regulating class specific dendrite morphogenesis in Drosophila.
abstract: BACKGROUND
  Dendritic morphology largely determines patterns of synaptic connectivity and electrochemical properties of a neuron. Neurons display a myriad diversity of dendritic geometries which serve as a basis for functional classification. Several types of molecules have recently been identified which regulate dendrite morphology by acting at the levels of transcriptional regulation, direct interactions with the cytoskeleton and organelles, and cell surface interactions. Although there has been substantial progress in understanding the molecular mechanisms of dendrite morphogenesis, the specification of class-specific dendritic arbors remains largely unexplained. Furthermore, the presence of numerous regulators suggests that they must work in concert. However, presently, few genetic pathways regulating dendrite development have been defined.
  
  
  RESULTS
  The Drosophila gene turtle belongs to an evolutionarily conserved class of immunoglobulin superfamily members found in the nervous systems of diverse organisms. We demonstrate that Turtle is differentially expressed in Drosophila da neurons. Moreover, MARCM analyses reveal Turtle acts cell autonomously to exert class specific effects on dendritic growth and/or branching in da neuron subclasses. Using transgenic overexpression of different Turtle isoforms, we find context-dependent, isoform-specific effects on mediating dendritic branching in class II, III and IV da neurons. Finally, we demonstrate via chromatin immunoprecipitation, qPCR, and immunohistochemistry analyses that Turtle expression is positively regulated by the Cut homeodomain transcription factor and via genetic interaction studies that Turtle is downstream effector of Cut-mediated regulation of da neuron dendrite morphology.
  
  
  CONCLUSIONS
  Our findings reveal that Turtle proteins differentially regulate the acquisition of class-specific dendrite morphologies. In addition, we have established a transcriptional regulatory interaction between Cut and Turtle, representing a novel pathway for mediating class specific dendrite development.
authors.affiliation: School of Systems Biology, George Mason University, Manassas, Virginia, United States of America.
authors.forename: Mikolaj J
authors.initials: MJ
authors.lastname: Sulkowski
authors.forename: Srividya Chandramouli
authors.initials: SC
authors.lastname: Iyer
authors.forename: Mathieu S
authors.initials: MS
authors.lastname: Kurosawa
authors.forename: Eswar Prasad R
authors.initials: EP
authors.lastname: Iyer
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Cox
mesh_terms: D000818:Animals; D003712:Dendrites / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism*; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009024:Morphogenesis; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D007136:Immunoglobulins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D014157:Transcription Factors; C066381:ct protein, Drosophila; C427323:tutl protein, Drosophila