The Thanos Requirement for Transdetermination Leads to an End Game on Wing Cell Fate as Ectopic Eyes Develop
Authors: Alison Smith; Justin Kumar
Affiliation: Indiana University Bloomington
Keywords: n. tissue specification; i. other imaginal discs
As development begins cells are in a pluripotent state, but via cell signaling pathways and morphogen concentration gradients cells begin to determine towards their final cell fate. Various developmental anomalies arise when a cell does not adopt or retain its correct fate. A process where a determined cell switches its fate to that of another without dedifferentiation is via transdetermination. Transdetermination can be studied in Drosophila via ectopic eye formation. Ectopic eyes can be formed through the misexpression of the master regulator gene of the retinal determination network eyeless (ey). Though it is more complex than a wing imaginal disc’s cell immediately switching its fate to that of a retinal fate solely with the initiation of ey misexpression. There are also certain requirements that must be met - the Thanos requirement. The Thanos requirement has five pillars including: spatial misexpression, co-expression of Dpp, magnitude of misexpression, initiation and duration of ey misexpression. I hypothesize that during this transdetermination as the cells move from their wing fate to that of retinal fate the cells proceed through a biphasic state where the cell is not solely fated as either wing or retinal. This is hypothesized due to my work using the UAS-GAL4 misexpression system. With this system I uncovered a previously undiscovered pillar of the Thanos requirement: duration of ey misexpression. This uninvestigated requirement is as follows, for an ectopic eye to form there must be GAL4 expression to drive eymisexpression not only in the wing disc but also the in the eye field of the eye antennal disc. This is such that as the cells begin to take on a more retinal fate than wing if the GAL4 driver is active in only the wing imaginal disc it will turn off, ceasing ey misexpression and no ectopic eye will form. Though if the GAL4 driver is active in both the wing imaginal disc and the eye antennal disc even as the cell takes on a more retinal fate the GAL4 enhancer will remain on, ey misexpression will continue, and an ectopic eye will form (if the four other pillars are also met). In the cases where all of the five pillars of the Thanos requirement are met there is an end game on wing fate as the cells adopt their new retinal state. I am further investigating the Thanos requirement using immunofluorescence and quantitative PCR. By understanding the requirement of transdetermination we may better understand the mechanism of transdetermination. By better understanding the mechanism of transdetermination we can not only gain a better understanding of cell fate determination, but what goes awry when cells switch their fates during development.