Optogenetic control of the Bicoid morphogen reveals fast and slow modes of gap gene regulation.

TitleOptogenetic control of the Bicoid morphogen reveals fast and slow modes of gap gene regulation.
Publication TypeJournal Article
Year of Publication2022
AuthorsSingh, AP, Wu, P, Ryabichko, S, Raimundo, J, Swan, M, Wieschaus, E, Gregor, T, Toettcher, JE
JournalCell Rep
Volume38
Issue12
Pagination110543
Date Published2022 03 22
ISSN2211-1247
KeywordsDrosophila Proteins, Gene Expression Regulation, Developmental, Homeodomain Proteins, Optogenetics, Trans-Activators
Abstract

<p>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.</p>

DOI10.1016/j.celrep.2022.110543
Alternate JournalCell Rep
PubMed ID35320726
PubMed Central IDPMC9019726
Grant ListR01 GM097275 / GM / NIGMS NIH HHS / United States
T32 GM007388 / GM / NIGMS NIH HHS / United States
U01 DA047730 / DA / NIDA NIH HHS / United States
U01 DK127429 / DK / NIDDK NIH HHS / United States