Overexpression of Rheb, a positive Tor regulator, reveals principles of rod outer segment size control

Abstract

AbstractThe outer segment of retinal rod photoreceptors is a highly modified cilium with the typical ciliary microtubular axoneme but additionally there are hundreds of densely packed, stacked, discrete intramembranous discs containing phototransduction machinery. The outer segment is continuously regenerated or renewed throughout the life of the animal through the combined processes of proximal growth and distal shedding. Since the pioneering experiments decades ago that demonstrated the process of rod outer segment renewal very little research has been directed towards understanding mechanistic principles of renewal and homeostasis, and many important questions remain unaddressed. The rod outer segment is a prime example of tight size control that is amenable to experimental and computational analyses. This study uses zebrafish molecular genetics with high resolution imaging, quantitative analyses, and computational modeling to uncover principles that regulate rod outer segment homeostatic length control. By genetically increasing rod outer segment growth, we show that outer segments lengthen and shedding does not accelerate to offset this added growth.