575A Poster - 08. Patterning, morphogenesis and organogenesis
Thursday April 07, 2:00 PM - 4:00 PM
Hh signaling coordinates stereotyped and stochastic patterns in the Drosophila eye
Authors: Alison Ordway; Caitlin Anderson; Lukas Voortman; Elizabeth Urban; Robert Johnston
Affiliation: Johns Hopkins University
Keywords: f. eye disc; c. activators/coactivators
Development of an organism requires both stereotyped and stochastic patterning. Stereotyped patterning robustly generates nearly identical structures across individuals. In contrast, stochastic cell fate specification produces randomized patterns that are unique to each individual. Stochastic fate decisions are required for the development of many sensory organs, including visual and olfactory systems. Despite their importance, how the molecular mechanisms controlling stereotyped and random patterns intersect within the same tissue has not been addressed. This project aims to determine how gene regulatory mechanisms are tuned to generate both highly regular and stochastic patterns within the same tissue using the Drosophila eye as a model.
The Drosophila eye is composed of ~800 ommatidia in a near perfect array. Each ommatidium comprises eight photoreceptors (R1-8) which develop in a predictable fashion. As photoreceptors are differentiating during larval eye development, a wave of morphogenesis driven by Hedgehog (Hh) signaling promotes the highly reproducible structure of the eye.
Underlying the uniform morphology of the fly eye is a random pattern of photoreceptor subtypes. Two R7 photoreceptor subtypes are defined by expression of light-detecting Rhodopsin proteins. Random patterning of these two R7 subtypes is controlled by stochastic ON/OFF expression of the transcription factor, Spineless (Ss). SsON R7s express Rhodopsin 4 (Rh4), whereas SsOFF R7s express Rhodopsin 3 (Rh3). ss is regulated by an interplay of transcription and chromatin regulation during larval eye development.
I found that Hh signaling plays a second role in eye development to regulate stochastic patterning. hh mutants display a reduction in the percentage of SsON R7s. Cubitus Interruptus (Ci), an effector of Hh signaling, binds at an eye specific enhancer in ss. This site overlaps with a binding site for Klumpfuss (Klu), a repressor of ss, suggesting competitive binding and regulation.
These results indicate that Hh signaling is finely tuned to drive both stereotyped eye morphology and generate stochastic R7 subtype patterning during development. My ongoing work aims to determine how Hh regulates transcription and chromatin compaction at the ss locus. I am also working to determine how Ci and Klu compete for binding and regulation of stochastic ss expression. My studies will describe how regulation of stochastic and stereotyped patterning is coordinated in a single developing tissue.