Innexin Gap Junctions

Normal brain glia development requires Ogre protein



Brain glial architecture is defective in an ogre mutant

Figure legend: The image panels above show cortex and neuropile glial cells in a wild type (top panels) and an ogre mutant (Image: ogre mutant genotype)(bottom panels) brain at three different planes through a region corresponding to the dashed box in the brain illustration above. In all images glia are expressing UAS-mCD8:GFP (green) reporter under the transcriptional control of the nrv2-GAL4 enhancer trap line (Sun et al, 1999). Panels on the left focus on the mushroom body lobes (Image: Mushroom body structure). Hovering the mouse over the image should highlight mushroom body lobes and the pedunculus in cross-section. Arrows point to differences between the normal and mutant brains (compare upper panels with the corresponding lower panel). Glia enshreathing the mushroom body lobes and pedunculus are severely reduced or absent in the ogre mutant. Neuropile glia processes are present in the mutant brain but they tend to aggregate at the brain midline (more obvious in the anterior and mid-brain panels). The cortex glia 'honeycomb' structure near the brain periphery can also be disrupted in the mutant (right panels) and cortex glial processes can accumulate mCD8:GFP reporter, producing intensely fluorescent spots (arrow, lower right panel). Size bars = 20μm.


What do these mutant phenotypes tell us?

  • Glial cells require normal levels of gap junction protein(s) for proper development. This is not unanticipated as connexins have been known for some time to have an important role in vertebrate glia. For example, the absence of glial connexin 32 (Cx32) results in defective myelinating Schwann cells (Bergoffen et al. 1993) and can also result in defects in glial-rich white matter regions of the human brain (Hanemann et al. 2003, Panas et al. 1998).
  • Does the absence of innexins result in glial cell death? The neuropile glial processes that fail to properly ensheath mushroom body structures in the ogre mutant might not be absent due to cell death, instead they may just be mislocalised, accumulating at the brain midline leading to the high levels of mCD8-GFP fluorescence detectable at the midline of ogre mutant brains. It is possible that Ogre protein is not required for glial cell differentiation/proliferation or survival but is instead required for correct guidance/targeting/adhesiveness of glial processes. Counting the number of glial cell bodies and noting their position in ogre mutant brains would go some way to addressing whether cell death/differentiation/proliferation are disrupted in the mutant.
  • If Ogre protein is involved in glial guidance/targeting, does this require signalling through gap junctions or is Ogre mainly required for cell adhesion? Loss of Ogre protein in ogre mutant glia does not necessarily mean that gap junctions fail to form. At least two other innexins are present in these cells, Inx2 + Inx3, and together these could faciliate cell-cell coupling in the absence of Ogre (Stebbings et al. 2000). It seems unlikely though, that Ogre protein might be required mainly for cell adhesion....?

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