Stochastic De-repression of Rhodopsins in Single Photoreceptors of the Fly Retina

Pranidhi Sood, Robert J Johnston and Edo Kussell

PLOS Computational Biology, 2012, vol. 8, issue 2, 1-13

Abstract: The photoreceptors of the Drosophila compound eye are a classical model for studying cell fate specification. Photoreceptors (PRs) are organized in bundles of eight cells with two major types – inner PRs involved in color vision and outer PRs involved in motion detection. In wild type flies, most PRs express a single type of Rhodopsin (Rh): inner PRs express either Rh3, Rh4, Rh5 or Rh6 and outer PRs express Rh1. In outer PRs, the K50 homeodomain protein Dve is a key repressor that acts to ensure exclusive Rh expression. Loss of Dve results in de-repression of Rhodopsins in outer PRs, and leads to a wide distribution of expression levels. To quantify these effects, we introduce an automated image analysis method to measure Rhodopsin levels at the single cell level in 3D confocal stacks. Our sensitive methodology reveals cell-specific differences in Rhodopsin distributions among the outer PRs, observed over a developmental time course. We show that Rhodopsin distributions are consistent with a two-state model of gene expression, in which cells can be in either high or basal states of Rhodopsin production. Our model identifies a significant role of post-transcriptional regulation in establishing the two distinct states. The timescale for interconversion between basal and high states is shown to be on the order of days. Our results indicate that even in the absence of Dve, the Rhodopsin regulatory network can maintain highly stable states. We propose that the role of Dve in outer PRs is to buffer against rare fluctuations in this network. Author Summary: Complex networks of genetic interactions govern the development of multicellular organisms. One of the best-characterized networks governs the development of the fruit-fly retina, a highly organized, three-dimensional organ composed of a hexagonal grid of eight types of photoreceptor neurons. Each photoreceptor responds to a particular wavelength of light depending on the Rhodopsin protein it expresses. We present novel computational methods to quantify cell-specific Rhodopsin levels from confocal microscopy images. We apply these methods to study the effect of the loss of a key repressor that ensures each photoreceptor expresses only one Rhodopsin. We show that this perturbation has cell-specific effects. Our measurement of the cell-type specific Rhodopsin distributions reveals differences between photoreceptor cells, which could not otherwise be detected. Using mathematical models of gene expression, we attribute this variability to stochastic events that activate Rhodopsin production.

Date: 2012
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1002357 (text/html)
https://journals.plos.org/ploscompbiol/article/fil ... 02357&type=printable (application/pdf)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:plo:pcbi00:1002357

DOI: 10.1371/journal.pcbi.1002357

Access Statistics for this article

More articles in PLOS Computational Biology from Public Library of Science
Bibliographic data for series maintained by ploscompbiol ().