Abstract

BackgroundThe retinal determination (RD) network is an evolutionarily conserved regulatory circuit that governs early events in the development of eyes throughout the animal kingdom. Ectopic expression of many members of this network leads to the transformation of non-retinal epithelia into eye tissue. An often-overlooked observation is that only particular cell-populations within a handful of tissues are capable of having their primary developmental instructions superseded and overruled.Methodology/Preliminary FindingsHere we confirm that indeed, only a discrete number of cell populations within the imaginal discs that give rise to the head, antenna, legs, wings and halteres have the cellular plasticity to have their developmental fates altered. In contrast to previous reports, we find that all transformable cell populations do not lie within the TGFβ or Hedgehog signaling domains. Additionally neither signaling cascade alone is sufficient for non-retinal cell types to be converted into retinal tissue. The transformation “hot spots” that we have identified appear to coincide with several previously defined transdetermination “weak spots”, suggesting that ectopic eye formation is less the result of one network overriding the orders of another, as previously thought, but rather is the physical manifestation of redirecting cell populations of enormous cellular plasticity. We also demonstrate that the initiation of eye formation in non-retinal tissues occurs asynchronously compared to that of the normal eye suggesting that retinal development is not under the control of a global developmental clock.Conclusions/SignificanceWe conclude that the subregions of non-retinal tissues that are capable of supporting eye formation represent specialized cell-populations that have a different level of plasticity than other cells within these tissues and may be the founder cells of each tissue.

Highlights

  • The retinal determination (RD) network is an evolutionarily conserved regulatory circuit that governs early events in the development of eyes throughout the animal kingdom

  • While a series of reports have documented the induction of ectopic eyes by members of the RD network [2,4,5,6,7,8,9,10,11,12] little comment, save two exceptions [14,17], has focused on the observed spatial constraints surrounding the transformation of non-retinal epithelia into eye tissue

  • We present evidence for an alternative hypothesis: that there are a discrete number of cell populations that are of sufficient developmental plasticity to have their primary developmental instructions superseded and thereby allowing for the adoption of a retinal fate

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Summary

Introduction

The retinal determination (RD) network is an evolutionarily conserved regulatory circuit that governs early events in the development of eyes throughout the animal kingdom. In Drosophila, removal of individual RD genes leads to an inhibition of eye formation while forced expression of these genes is sufficient to redirect the fate of non-retinal tissues [1]. The Pax6/eyeless (ey) gene exemplifies these characteristics as ey mutants have retinal defects that range from partial to complete loss of eye tissue. Ectopic expression induces eye formation in the imaginal discs that give rise to the developing antenna, legs, wings and halteres [2,3]. A complete understanding of the mechanisms that promote and restrict eye formation to specific cell populations and tissues remains elusive. Ectopic expression of many members of this network leads to the transformation of non-retinal epithelia into eye tissue. An often-overlooked observation is that only particular cell-populations within a handful of tissues are capable of having their primary developmental instructions superseded and overruled

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