A mechanism for hunchback promoters to readout morphogenetic positional information in less than a minute

Abstract

Cell fate decisions in the fly embryo are rapid: hunchback genes decide in minutes whether nuclei follow the anterior/posterior developmental blueprint by reading out positional information in the Bicoid morphogen. This developmental system is a prototype of regulatory decision processes that combine speed and accuracy. Traditional arguments based on fixed-time sampling of Bicoid concentration indicate that an accurate readout is impossible within the experimental times. This raises the general issue of how speed-accuracy tradeoffs are achieved. Here, we compare fixed-time to on-the-fly decisions, based on comparing the likelihoods of anterior/posterior locations. We found that these more efficient schemes complete reliable cell fate decisions within the short embryological timescales. We discuss the influence of promoter architectures on decision times and error rates, present concrete examples that rapidly readout the morphogen, and predictions for new experiments. Lastly, we suggest a simple mechanism for RNA production and degradation that approximates the log-likelihood function.

Defining kinetic roles of transcriptional activators in the early Drosophila embryo

“…Choosing a model to describe the first passage distributions has been challenging (Desponds et al, 2020;Dufourt et al, 2018;Eck et al, 2020) . One approach has been to ignore the time delay following the end of anaphase and only consider the first passage times once transcription has been detected in any nucleus across the entire pattern (as in (Dufourt et al, 2018) ).…”

“…Many studies have measured transcription in the embryo using the MS2/MCP system (reviewed in (Fernandez and Lagha, 2019;Wissink et al, 2019) ).The analytical approaches employed by these studies range from statistical quantification (e.g. (Fukaya et al, 2016;Yamada et al, 2019) ) to various mathematical models (Bothma et al, 2015;Desponds et al, 2016Desponds et al, , 2020Dufourt et al, 2018;Eck et al, 2020;Keller et al, 2020;Lammers et al, 2020) . However, the MS2/MCP measurements themselves are many biochemical steps removed from the molecular kinetics of interest, namely transcription initiation.…”

Dynamic patterning by morphogens illuminated by cis-regulatory studies

“…Bcd can affect target gene expression even in posterior regions, where the gradient is more diffuse, by forming local hubs within nuclei that are concentrated enough to facilitate Bcd binding to enhancers (Mir et al, 2017). Furthermore, despite the short time that Bcd molecules are bound to DNA (Mir et al, 2018), this input is translated into accurate and fast gene expression decisions at target enhancers that occur on the timescale of a few minutes (Desponds et al, 2020). Together, these mechanisms that regulate the distribution of Bcd in the embryo and its interaction with target enhancers determine the ability of this morphogen to differentially affect gene expression across the AP axis.…”

Bacteriophage self-counting in the presence of viral replication

“…Consequently, viral replication is found to facilitate, rather than hinder, the implementation of a reliable decision. Since cellular decisions frequently take place even as gene copy number is changing (Desponds et al, 2020; Hwang et al, 2017; Weinberger, 2015), this inextricable coupling of gene dosage and network output cannot be ignored if one aims for a predictive description of cellular decision making.…”