Rapid transcriptional response to a dynamic morphogen by time integration.

During development, cells must interpret extracellular signals with speed and accuracy. While morphogen gradients pattern tissues, how cells respond to dynamic morphogens remains unclear. Here, we investigate how dorsal patterning in the Drosophila embryo is specified by a rapidly evolving BMP gradient. Using a live reporter of BMP pathway activity and nascent transcription reporters, we find that gene expression is best predicted by time integration of BMP signaling, rather than instantaneous levels. We show that the transcription factor Zen lowers the signaling threshold required for activation, enabling integration to drive rapid transcriptional responses even at low BMP levels. We tested our integration model using mutants that alter BMP signaling dynamics. Within the normal expression domain, integration was still predictive of gene expression. However, higher levels of integrated signaling were needed in more lateral regions of the embryo, suggesting additional spatial patterning regulation. Together, these results suggest that cells interpret dynamic morphogen signals through the combined action of temporal integration and spatial competence, providing a framework for robust pattern formation on fast developmental timescales.

Duke Scholars

Author Stefano Di Talia Cell Biology

Author Susanna Brantley