Innexin Gap Junctions

Genetic manipulation of innexins has developmental consequences

Image comparing antennae from wild type and mutant Inx2 flies

Figure legend: Mutation of endogenous innexin genes can disrupt the normal developmental program. The left panel above shows an antenna belonging to a wild type Drosophila. The arista (arrow) is long, thin and branched. The panel on the right shows an antenna from a dominant innexin mutant Inx2TA181 (originally called StoutTA181 Florence and McGinnis, 1998, see: inx2 summary). Development of the arista has been disrupted resulting in a club-shaped structure. This phenotype can be observed in all animals carrying the mutation.

Image showing wing phenotypes induced by innexin subunit overexpression

Figure legend: Transgenic methods can also be employed to study the role of gap junctions in development. The image above shows three adult Drosophila. Top panel: a wild type (wt) animal for comparison. Left panel: an animal that over-expressed Ogre in the developing wing (sdGAL4/UAS-ogre) resulting in loss of nearly all of the wing blade tissue. Right panel: an animal that over-expressed Inx7 in the developing wing (ptcGAL4/UAS-inx7) leading to blistered, often fluid-filled, wings that lack marginal wing blade material.

Genetics and the study of gap junctions in Drosophila

Drosophila melanogaster is a model genetic organism that can be employed to identify genes that interact with gap junctions without having any a priori knowledge of what the interactor genes might be, or what biological roles gap junctions perform during development. The images shown above provide examples of phenotypes arising through abnormal development. Screening for mutations that modify these phenotypes (enhancer/suppressor screens, St. Johnston 2002) should identify genes that interact directly or indirectly with innexin molecules or at least with the 'process' of gap junction-mediated intercellular communication.
Dominant connexin mutants have previously been reported in the published literature and are often associated with human diseases (Laird, 2008, Yan et al. 2008). The types of mutation giving rise to dominant gap junction mutants, and the mechanisms underlying their phenotypes, should be easier to investigate now that they are known to exist in a model genetic organism. The results of this analysis may highlight important similarity, or possibly divergence, between connexin- and innexin-based gap junctions.

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