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Alaron Lewis, Joseph Mahoney, Neil Wilson, Susan Brockerhoff; Examining the role of celsr3 in amacrine cell development in the zebrafish retina. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2493.
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We have identified celsr3, an atypical cadherin, as essential for normal inhibitory circuit formation in the inner retina. Its absence during retinal development leads to changes in GABA receptor numbers and retinal physiology without causing obvious cell spacing or synaptic lamination defects in the inner retina. This study focuses on determining the subset of amacrine and bipolar cells that express celsr3, and whether the loss of celsr3 results in subtle morphological defects in these cells.
We have developed a BAC transgene expressing EGFP under the control of the celsr3 promoter (Tg(Celsr3::EGFP )). We inject one-cell zebrafish embryos with the transgene and analyze celrs3 expressing amacrine and bipolar cell morphology at 5 dpf in mosaic larvae using confocal microscopy. Cells are categorized based on shape, arborization and lamination.
The expression of our transgene recapitulates our in situ data. In the retina the transgene is expressed in ganglion, amacrine and bipolar cells. We have defined several classes of amacrine and bipolar cells that express Tg(Celsr3::EGFP ). These include several classes of mono-stratified amacrine cells, and a number of small bushy amacrine cells. We are currently working to determine if the characteristics of these cells are altered in a celsr3 mutant zebrafish.
We propose that celsr3 represents an undiscovered class of molecules that are important for normal development of GABAergic pathways in the inner retina, but do not strongly affect inner plexiform layer lamination. Disruptions in inhibitory circuits have been implicated in many neurological disorders such as Alzheimer’s, autism, epilepsy and schizophrenia. One exciting idea is that research in the area of inhibitor circuit formation and regulation will lead to the ability to modulate GABA transmission and thereby treat diseased nervous systems.
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