OPTOGENETIC CONTROL OF BICOID MORPHOGEN IN THE DROSOPHILA EMBRYO

Abstract

During development, naïve cells adopt different fate and form complex structure in defined spatial arrangement and temporal order. The spatial organization of cell fates involves interpretation of gradients and differential gene expression. The gap gene network transforms rudimentary positional cues into a multitude of sharply defined domains of gene expression, playing an essential role in pattern formation during early Drosophila embryonic development. The redundant inputs and intricate feedbacks in the network ensure the precision and robustness of cell fate decision and pattern formation. Meanwhile, it also prevents us from further understanding the specific regulations and network topology. By reducing the complexity of the network and perturbing one input rapidly via optogenetics with live-recording of both input and output, we are able to dissect the contribution from one transcription factor – Bicoid. Our results recapitulate the direct activation of gt and hb by Bicoid and the indirect regulation of Kr. Additionally, we also uncover a noncanonical direct repressive role for Bicoid, where kni exhibits a rapid and inverted response to acute Bicoid perturbation. Our findings demonstrate that rapid perturbation while simultaneously recording of the response can provide a powerful approach to investigate the dynamic gap network and can be potentially generalized to study other gene networks.