Time to move on: Modeling transcription dynamics during an embryonic transition away from maternal control

Zhu

Kong

et al. 2020

eLife

It has been suggested that Staufen (Stau) is key in controlling the variability of the posterior boundary of the Hb anterior domain (xHb). However, the mechanism that underlies this control is elusive. Here, we quantified the dynamic 3D expression of segmentation genes in Drosophila embryos. With improved control of measurement errors, we show that the xHb of stau– mutants reproducibly moves posteriorly by 10% of the embryo length (EL) to the wild type (WT) position in the nuclear cycle (nc) 14, and that its variability over short time windows is comparable to that of the WT. Moreover, for stau– mutants, the upstream Bicoid (Bcd) gradients show equivalent relative intensity noise to that of the WT in nc12–nc14, and the downstream Even-skipped (Eve) and cephalic furrow (CF) show the same positional errors as these factors in WT. Our results indicate that threshold-dependent activation and self-organized filtering are not mutually exclusive and could both be implemented in early Drosophila embryogenesis.

Section: Resultsmentioning

confidence: 99%

The dynamic transmission of positional information in stau- mutants during Drosophila embryogenesis

Zhu

Kong

et al. 2020

eLife

“…A novel F-box protein named fates-shifted (ftd) was reported to play a role in degrading Bcd, which is important in shaping the Bcd gradient [85]. Gene dmpd and sumo were discovered to advance and delay the shutdown of the Bcd dependent transcription of hb at early nc14, respectively [86,87]. The endo-siRNA pathway was found to be essential to maintain the robustness of the patterning against the temperature fluctuations.…”

Section: Discussionmentioning

confidence: 99%

“…More importantly, to fully capture the dynamics of the development system, the model needs to emphasize time-dependent transient behaviors, instead of the steady state or a random snapshot. Since the dynamics is associated with temporal-variable inputs (e.g., the dynamics of Bcd gradients [2,20]) and the temporal coordinated regulatory switches (e.g., the switch-off of Bcd-dependent hb expression at the beginning of nc14 [86]), it could be better to be accounted by the non-autonomous models with explicit time-dependent parameter changes [86]. On the other hand, mathematical models grounded in physics starts to serve as the " Figure 1 theory" instead of the " Figure 7 theory" in studying biological systems [88], i.e., providing new concepts to direct new testable experiments instead of solely supporting the existing experimental results.…”

Section: Discussionmentioning

confidence: 99%

Noise transmission during the dynamic pattern formation in fly embryos

et al. 2018

Quant. Biol.

Background: Developmental patterning is highly reproducible and accurate at the single-cell level during fly embryogenesis despite the gene expression noise and external perturbations such as the variation of the embryo length, temperature and genes. To reveal the underlying mechanism, it is very important to characterize the noise transmission during the dynamic pattern formation. Two hypotheses have been proposed. The "channel" scenario requires a highly reproducible input and an accurate interpretation by downstream genes. In contrast, the "filter" scenario proposes a noisy input and a noise filter via the cross-regulation of the downstream network. It has been under great debates which scenario the fly embryogenesis follows. Results: The first 3-h developmental patterning of fly embryos is orchestrated by a hierarchical segmentation gene network, which rewires upon the maternal to zygotic transition. Starting from the highly reproducible maternal gradients, the positional information is refined to the single-cell precision through the highly dynamical evolved zygotic gene expression profiles. Thus the fly embryo development might strictly fit into neither the originally proposed "filter" nor "channel" scenario. The controversy that which scenario the fly embryogenesis follows could be further clarified by combining quantitative measurements and modeling. Conclusions: Fly embryos have become one of the perfect model systems for quantitative systems biology studies. The underlying mechanism discovered from fly embryogenesis will deepen our understanding of the noise control of the gene network, facilitate searching for more efficient and safer methods for cell programming and reprogramming, and have the great potential for tissue engineering and regenerative medicine.Keywords: pattern formation; gene regulatory network; noise; embryogenesis; Drosophila Author summary: It is intriguing how the development of organisms is highly reproducible and accurate despite the external and internal noise. The key to solve this mystery is to explore the noise transmission during development and discover the underlying mechanism. The developmental system could generate precise inputs and outputs in each step, or gradually generate a final precise output by filtering a noisy input according to the "channel" or "filter" scenario, respectively. The quantitative studies on the early development of the fruit fly's embryos show that the developmental process is highly dynamic and its noise transmission may employ a hybridized strategy.

“…Another concern is that Bcd-dependent Hb expression turns off in less than 10 min into nc14 (Liu and Ma, 2013;Liu et al, 2016), and the time window for Bcd interpretation could be earlier than nc14 (Huang et al, 2017;(Bergmann et al, 2007), hence Hb expression could be largely obtained by translating the previously produced mRNA. It is therefore necessary to measure the dynamic Bcd gradient noise in developmental time earlier than the conventional measurement time, i.e., 16 min into nc14.…”

Section: A Large Dynamic Shift In the Hb Boundary Of Staumutantsmentioning

confidence: 99%

The dynamic transmission of positional information in stau^- mutants during Drosophila embryogenesis

Zhu

Kong

et al. 2019

Preprint

Intriguingly, the developmental patterning during Drosophila embryogenesis is highly accurate and robust despite its dynamic changes and constant fluctuations. It has been suggested that Staufen (Stau) is key in controlling the boundary variability of the gap protein Hunchback (Hb). However, its underlying mechanism is still elusive. Here, we have developed methods to quantify the dynamic 3D expression of segmentation genes in Drosophila embryos. With improved control of measurement errors, our results reveal that the posterior boundary of the Hb anterior domain (x Hb ) of staumutants shows comparable variability to that of the wild type (WT) and shifts posteriorly by nearly 12% of the embryo length (EL) to the WT position in the nuclear cycle (nc) 14. This observed large shift might contribute significantly to the apparent large variability of x Hb in previous studies. Moreover, for staumutants, the upstream Bicoid (Bcd) gradients show equivalent gradient noise to that of the WT in nc12-nc14, and the downstream Evenskipped (Eve) and cephalic furrow (CF) show the same positional errors as the WT. Our results indicate that threshold-dependent activation and self-organized filtering are not mutually exclusive but could both be implemented in early Drosophila embryogenesis.