Optogenetic control of the Bicoid morphogen reveals fast and slow modes of gap gene regulation. Author Anand Singh, Ping Wu, Sergey Ryabichko, João Raimundo, Michael Swan, Eric Wieschaus, Thomas Gregor, Jared Toettcher Publication Year 2022 Type Journal Article Abstract 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 Krüppel. 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. Keywords Trans-Activators, Drosophila Proteins, Gene Expression Regulation, Developmental, Optogenetics, Homeodomain Proteins Journal Cell Rep Volume 38 Issue 12 Pages 110543 Date Published 2022 Mar 22 ISSN Number 2211-1247 DOI 10.1016/j.celrep.2022.110543 Alternate Journal Cell Rep PMCID PMC9019726 PMID 35320726 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML