Oscillatory Hedgehog signaling and temporal coordination of atonal dynamics at the eye differentiation front in Drosophila

Pattern formation in the Drosophila eye involves the pulsatile expression of the proneural gene atonal (ato) and the periodic activation of Notch. Oscillatory expression of the ato gene results from the synchronous activation of two distinct ato enhancers that are active in two adjacent rows of cell clusters along the front of differentiation. How synchronous enhancer activation is achieved along the front is not known. Hedgehog (Hh) is a diffusive signal produced just posterior to the front which contributes to regulate ato gene expression. Here, we find that both ato enhancers are regulated by Hh and that two Hh target genes, patched (ptc) and decapentaplegic (dpp), are expressed at the front of differentiation in an oscillatory manner downstream of a constant Hh signal. Consistent with a role of Hh in the temporal coordination of ato gene expression along the front, lowering Hh activity was associated with pattern irregularities along the front. We propose a model whereby the periodic expression of the Hh receptor Ptc under the control of pulsatile Ato and/or Notch dynamics produces rhythmic changes in extracellular Hh which would in turn coordinate ato dynamics locally. In this model, oscillatory Hh would provide a temporal cue to coordinate patterning dynamics along the front of differentiation in the developing eye.