Cadherin Functions In Other Systems

As with vertebrates, a-cadherin synaptogenic functions are the most widely characterized among cadherin family members in Drosophila, mainly based on analyses of mosaic fly embryos. Initially, all cells in these flies carry one copy of a gene of interest that has been disrupted by insertion of a reporter gene that also has recombination elements. Cells within a distinct subset also carry a second mutation that allows heat-inducible mitotic recombination such that, upon transferring these embryos to the permissive temperature, homozygous mutations are generated in a particular class of cells. This manipulation allows distinct neurons to be mutated with some temporal control and these mutant neurons to be visualized in a comparatively normal (i.e. "wild-type") background.

a-cadherin function has been examined by this type of mosaic analysis foremost in the fly olfactory system. Olfactory receptor neurons (ORNs) in the sensory neuropil send primary axons to the dendrites of projection neurons (PNs) at glomeruli in the antenna lobe. The dendritic arbors of individual PNs—which, at first, only loosely demarcate a protoglomerulus—become confined to form a single, more distinct glomerulus upon innervation by several ORNs, which themselves express the same, unique odorant receptor (OR) but are broadly distributed63. Normally, both ORN axons and PN dendrites express a-cadherin, but individual, mosaic PN dendrites homozygous for a null a-cadherin mutation fail to refine their arbors in response to wild-type ORN innervation or neighboring dendritic arbors63. By comparison, OR-specific ORN axons homozygous for either a null or inactivating a-cadherin mutation properly co-fasciculate and target the antenna lobe but fail to restrict their terminals to dendrites within a single protoglomerulus63,64. These findings suggest that, as in rat hippocampal neurons, a-cadherin does not encode target selectivity per se, but may mediate the selective strengthening of certain synapses within a network in response to activity.

This role also may hold true for the fly visual system. Normally, photoreceptors 1 through 6 (R1-6) from each ommatidium project according to subtype to stereotyped columns of laminar neurons—first the "column of origin," then the target column—within the optic neuropil. Instead, photoreceptors largely fail to project beyond their specific column of origin to lamina neurons in the target column when either lacks a-cadherin65. Although mosaic flies mutant for E-cadherin and other nonclassical cadherins had no obvious phenotypes in these contexts63,65, these latter family members are likely to serve other aspects of synapse formation or maturation in this system.

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