Modeling R8 Specification in the Drosophila Eye, from Genes to Tissue.

[摘要] Drosophila melanogaster, the fruit fly, has compound eyes consisting of around 750 facets called ommatidia, arranged in a regular hexagonal grid.Each facet is centered on a suite of 8 photoreceptor neurons (R1-R8), of which R8 is the first retinal cell to attain a specific fate.In this dissertation I present a multiscale model of R8 photoreceptor specification in the developing eye imaginal disc.This pattern-forming system is characterized by an expanding field of R8 cells arranged in a regular hexagonal pattern formed behind a wave of distortion and differentiation known as the morphogenetic furrow.The basic model consists of ordinary differential equations defined on a lattice representing a cellular epithelium, and is based on observed genetic interactions centered on the proneural transcription factor-encoding gene atonal.It includes cell-autonomous autoactivation, long-range diffusible activation, and shorter-range inhibition.Patterning very similar to that observed in the eye can be observed given appropriate choice of parameters and initial conditions.First, I examine a simplified version of the model analytically, explaining its basic behavior and exposing the multiscale nature of the process.If the propagation of the pattern is slow compared to the more local activity of cell differentiation, regular patterns with single R8 cells are generated reliably, and the system is very robust to parameter changes.Next, I investigate the system in restricted 2D cases.I find that the behavior of the system is well-explained for regimes of interest by starting with a simple case, and applying the results to successively more complex systems.Specifically, I characterize the model’s behavior at the levels of a single cell, two cells, several cells, and small patches of epithelium.I use these results to make specific predictions and to explain the patterning behavior of eye-discs.Lastly, I examine the application of modeling small groups of cells to long-range patterning.I accomplish this by approximating the overall system as a finite-state machine.This represents a new theory of neural fate specification in the eye disc, and provides an ample basis for future experimental and theoretical work.

[发布机构] University of Michigan

[效力级别] Eye Imaginal Disc

[关键词] Pattern Formation;Eye Imaginal Disc;Atonal;Drosophila Development;Activator-Inhibitor;Physics;Science;Biophysics