Mushroom body axons, and the nervous system in general, have been studied extensively in wild type and mutant Drosophila and some of these studies could provide insight into what is going wrong in ogre mutant flies. The table below summarizes the different axonal defect that are observed in ogre mutant mushroom body axons.
|Neuronal defect||Frequency observed||Similarities with published reports|
|Variable GFP intensity in mushroom body neurons||100%||May indicate that transcription in neurons is disrupted when glia are absent. This is quite likely as neurons respond to many glial signals (Dumstrei et al. 2003, Hidalgo, 2003).|
β/γ-lobe axons cross the brain midline
|Observed in a number of mutants of genes expressed in neurons or in glia (see text below this table). Possibly a cell signalling or axon guidance failure.|
|Thin or absent α lobes||62%||Mutation of neuronal cell adhesion molecules FasII (Kurusu et al. 2002) and Dscam (Zhan et al. 2004) produce similar phenotypes.|
|Punctate distribution of mCD8:GFP reporter||32%||Could this be a feature of axonal degeneration? Expression of gap junction proteins in glia promotes neuronal survival (Bergoffen et al. 1993). Loss of glia could prevent removal of neurotoxic molecules such as ions or glutamate (Rival et al. 2004) leading to neuronal degeneration.|
|Axonal outgrowth from tip of α lobe||Unquantified||Failure of glia to prune axons during metamorphosis can lead to axonal outgrowths (Awasaki and Ito, 2004).|
|Defasiculation of axonal clusters in the pedunculus||Unquantified||Disruption of glia in the embryonic CNS and in nerves of the PNS can result in axonal defasiculation (Zhou et al. 1997, Sepp and Auld, 2003).|
Many of the axonal phenotypes observed in ogre mutant mushroom bodies are similar to phenotypes that have been reported previously in the literature and, mostly, can be linked to absent or defective glia. However, until some lab does the appropriate experiments this remains conjecture. Some phenotypes, for example, the β/γ-lobe axons crossing the midline have been seen in mutants of neuronal genes; fasII ( Fasciclin II, homologue of N-CAM (Kurusu et al. 2002), lio (linotte also named derailed, atypical receptor tyrosine kinase (Moreau-Fauvarque et al. 1998), dfmr1 (Fragile X mental retardation 1, also called DFXR, an mRNA binding protein that inhibits translation (Morales et al. 2002), overexpression of eph (signal transduction (Boyle et al. 2006). Loss of Ogre protein and the corresponding defects in glial cells could result in abnormal transcription of these proteins in mushroom body neurons. Alternatively, a more direct link between this phenotype and glial cells may exist. Genetic ablation of Transient Interhemispheric Fibrous Ring (TIFR) glia results in medial lobes crossing the brain midline (Hitier et al. 2000). If Ogre is expressed, and required, in the TIFR glia during development, then disruption of glial function/morphology in ogre mutant pupal brains could give rise to the observed adult MB neuronal phenotypes. This may indeed be the case; Inx2 is observed in fibrous tracts traversing the pupal brain hemispheres (image showing Inx2 staining in the putative TIFR glia). We haven't tried detecting Ogre in these cells, but 'generally', many other tissues that express Inx2 usually also express Ogre.