RT Journal Article SR Electronic T1 Optogenetic control of the Bicoid morphogen reveals fast and slow modes of gap gene regulation JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.10.13.464280 DO 10.1101/2021.10.13.464280 A1 Singh, Anand P. A1 Wu, Ping A1 Ryabichko, Sergey A1 Raimundo, João A1 Swan, Michael A1 Wieschaus, Eric A1 Gregor, Thomas A1 Toettcher, Jared E. YR 2021 UL http://biorxiv.org/content/early/2021/10/14/2021.10.13.464280.abstract AB 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 quantitative regulatory dynamics from a complex genetic network in vivo. We engineer light-controlled variants of the Bicoid transcription factor and study their effects on downstream gap genes in embryos. Our results recapitulate known relationships, including rapid Bicoid-dependent expression of giant and hunchback and delayed repression of Krüppel. In contrast, we find that the posterior pattern of knirps exhibits a quick but inverted response to Bicoid perturbation, suggesting a previously unreported role for Bicoid in suppressing knirps expression. Acute modulation of transcription factor concentration while simultaneously recording output gene activity represents a powerful approach for studying how gene circuit elements are coupled to cell identification and complex body pattern formation in vivo.Competing Interest StatementThe authors have declared no competing interest.