title: The cytoskeletal regulator Genghis khan is required for columnar target specificity in the Drosophila visual system.
abstract: A defining characteristic of neuronal cell type is the growth of axons and dendrites into specific layers and columns of the brain. Although differences in cell surface receptors and adhesion molecules are known to cause differences in synaptic specificity, differences in downstream signaling mechanisms that determine cell type-appropriate targeting patterns are unknown. Using a forward genetic screen in Drosophila, we identify the GTPase effector Genghis khan (Gek) as playing a crucial role in the ability of a subset of photoreceptor (R cell) axons to innervate appropriate target columns. In particular, single-cell mosaic analyses demonstrate that R cell growth cones lacking Gek function grow to the appropriate ganglion, but frequently fail to innervate the correct target column. Further studies reveal that R cell axons lacking the activity of the small GTPase Cdc42 display similar defects, providing evidence that these proteins regulate a common set of processes. Gek is expressed in all R cells, and a detailed structure-function analysis reveals a set of regulatory domains with activities that restrict Gek function to the growth cone. Although Gek does not normally regulate layer-specific targeting, ectopic expression of Gek is sufficient to alter the targeting choices made by another R cell type, the targeting of which is normally Gek independent. Thus, specific regulation of cytoskeletal responses to targeting cues is necessary for cell type-appropriate synaptic specificity.
authors: Department of Neurobiology, 299 W. Campus Drive, Stanford University, Stanford, CA 94305, USA.
authors: Allison C
authors: AC
authors: Gontang
authors: Jennifer J
authors: JJ
authors: Hwa
authors: Joshua D
authors: JD
authors: Mast
authors: Tina
authors: T
authors: Schwabe
authors: Thomas R
authors: TR
authors: Clandinin
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D005123:Eye / Q000294:innervation*; D056726:Genetic Association Studies; D020439:Growth Cones / Q000378:metabolism / Q000502:physiology; D008954:Models, Biological; D009475:Neurons, Afferent / Q000378:metabolism / Q000502:physiology; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D012680:Sensitivity and Specificity; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology; D014785:Vision, Ocular / Q000235:genetics*; D014795:Visual Pathways / Q000378:metabolism / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; C109463:Gek protein, Drosophila; D017346:Protein Serine-Threonine Kinases