title: Genetic and Environmental Control of Neurodevelopmental Robustness in Drosophila.
abstract: Interindividual differences in neuronal wiring may contribute to behavioral individuality and affect susceptibility to neurological disorders. To investigate the causes and potential consequences of wiring variation in Drosophila melanogaster, we focused on a hemilineage of ventral nerve cord interneurons that exhibits morphological variability. We find that late-born subclasses of the 12A hemilineage are highly sensitive to genetic and environmental variation. Neurons in the second thoracic segment are particularly variable with regard to two developmental decisions, whereas its segmental homologs are more robust. This variability "hotspot" depends on Ultrabithorax expression in the 12A neurons, indicating variability is cell-intrinsic and under genetic control. 12A development is more variable and sensitive to temperature in long-established laboratory strains than in strains recently derived from the wild. Strains with a high frequency of one of the 12A variants also showed a high frequency of animals with delayed spontaneous flight initiation, whereas other wing-related behaviors did not show such a correlation and were thus not overtly affected by 12A variation. These results show that neurodevelopmental robustness is variable and under genetic control in Drosophila and suggest that the fly may serve as a model for identifying conserved gene pathways that stabilize wiring in stressful developmental environments. Moreover, some neuronal lineages are variation hotspots and thus may be more amenable to evolutionary change.
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Mellert
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, United States of America.
authors.forename: W Ryan
authors.initials: WR
authors.lastname: Williamson
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, United States of America.
authors.forename: Troy R
authors.initials: TR
authors.lastname: Shirangi
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, United States of America.
authors.forename: Gwyneth M
authors.initials: GM
authors.lastname: Card
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, United States of America.
authors.forename: James W
authors.initials: JW
authors.lastname: Truman
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D029721:Drosophila Proteins / Q000096:biosynthesis* / Q000235:genetics; D004331:Drosophila melanogaster; D005426:Flight, Animal / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D059647:Gene-Environment Interaction; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D055495:Neurogenesis / Q000502:physiology*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors; C066177:Ubx protein, Drosophila