Dynamic Hh signaling can generate temporal information during tissue patterning

Abstract

The differentiation of tissues and organs requires that cells exchange information in space and time. Spatial information is often conveyed by morphogens, molecules that disperse across receiving cells generating signaling gradients. Cells translate such concentration gradients into space-dependent patterns of gene expression and cellular behavior [1, 2]. But could morphogen gradients also convey developmental time? Here, investigating the developmental role of Hh on a component of the Drosophila visual system, the ocellar retina, we discovered that ocellar cells use the non-linear gradient of Hh as a temporal cue, collectively performing the biological equivalent of a mathematical logarithmic transformation. In this way, a morphogen diffusing from a non-moving source is decoded as a wave of differentiating photoreceptors that travels at constant speed throughout the retinal epithelium.

Patterning on the move: the effects of Hh morphogen source movement on signaling dynamics

“…We have measured previously that the characteristic length of the Hh exponential profile is around 13 µm and that is conserved for antenna, ocellus, compound eye and wing disk (Miguez et al, 2020). This value of Hh diffusion, combined with the value of Hh production at the source and degradation rates also result in a steady state configuration reached at around 60 min in the absence of other downstream interactions, which is consistent with our previous data (Garcia-Morales et al, 2019).…”

“…Immunolocalization and confocal microscopy was done as described in (Garcia-Morales et al, 2019). Antibodies used were: rabbit anti-GFP (A11122, at 1/1000; Molecular Probes); mouse anti-Ptc (Apa1; at 1/100) and rat anti-CiA (2A1; at 1/5) were obtained from the Developmental Studies Hybridoma Bank, created by the NICHD of the NIH and maintained at The University of Iowa, Department of Biology, Iowa City, USA.…”

“…Interestingly, Ptc is among the transcriptional targets of the pathway: cells receiving Hh up-regulate ptc expression (Figure 1; (Capdevila et al, 1994;Tabata and Kornberg, 1994). As a result of this feedback, increasing levels of Ptc, by binding to Hh, dynamically alter the quantitative profile of Hh across the field of Hh-receiving cells and modify the signaling levels in those cells (Briscoe et al, 2001;Garcia-Morales et al, 2019;Li et al, 2018;Miguez et al, 2020). Hh proteins are produced in specific domains within a developing organ and lay adjacent to Hh-responsive cells expressing ptc and ci.…”