Laboratory for the Physics of Life Thomas Gregor, Professor of Physics, Princeton University

Anand P. Singh, Ping Wu, Sergey Ryabichko, Joao Raimundo, Michael Swan, Eric Wieschaus,
Thomas Gregor, and Jared E. Toettcher (2022). Cell Reports 38, 110543.

Developmental patterning networks are regulated by multiple inputs and feedback connections that rapidly
reshape gene expression, limiting the information that can be gained solely from slow genetic perturbations.
Here we show that fast optogenetic stimuli, real-time transcriptional reporters, and a simplified genetic background can be combined to reveal the kinetics of gene expression downstream of a developmental transcription factor in vivo. We engineer light-controlled versions of the Bicoid transcription factor and study their
effects on downstream gap genes in embryos. Our results recapitulate known relationships, including rapid
Bicoid-dependent transcription of giant and hunchback and delayed repression of Kruppel € . In addition, we
find that the posterior pattern of knirps exhibits a quick but inverted response to Bicoid perturbation, suggesting a noncanonical role for Bicoid in directly suppressing knirps transcription. Acute modulation of
transcription factor concentration while recording output gene activity represents a powerful approach for
studying developmental gene networks in vivo.

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