TworibeyeGenes in Teleosts: The Role of Ribeye in Ribbon Formation and Bipolar Cell Development

Abstract

Ribeye is the only known protein specific to synaptic ribbon, but its function is unclear. We show that the teleost fish,Fuguand zebrafish, have tworibeyegenes,ribeye aand ribeyeb. Whole-mountin situhybridization revealed thatribeye ais expressed in tissues containing synaptic ribbons, including the pineal gland, inner ear, and retina.Ribeye bis absent in the pineal gland. In the retina,ribeye ais expressed in both photoreceptors and bipolar cells, whereasribeye bis detected only in photoreceptors. To study the function of Ribeye a in retina, we depleted it by morpholino antisense oligos. Fish deficient in Ribeye a lack an optokinetic response and have shorter synaptic ribbons in photoreceptors and fewer synaptic ribbons in bipolar cells. Their bipolar cells still target Syntaxin-3 proteins to the inner plexiform layer and have abundantvsx1mRNA. However, they lack large synaptic terminals and show increased apoptosis. Rod bipolar cells are fewer in number and/or deficient in PKCα. Recovery of Ribeye a levels rescues the optokinetic response, increases the number of PKCα-positive bipolar cells, and stops apoptosis. We conclude that Ribeye a is important for late steps in bipolar cell development.