A repressor-decay timer for robust temporal patterning in embryonic Drosophila neuroblast lineages
- Weizmann Institute of Science, Israel
- Howard Hughes Medical Institute, University of Oregon, United States
Abstract
Biological timers synchronize patterning processes during embryonic development. In the Drosophila embryo, neural progenitors (neuroblasts; NBs) produce a sequence of unique neurons whose identities depend on the sequential expression of temporal transcription factors (TTFs). The stereotypy and precision of NB lineages indicate reproducible TTF timer progression. We combine theory and experiments to define the timer mechanism. The TTF timer is commonly described as a relay of activators, but its regulatory circuit is also consistent with a repressor-decay timer, where TTF expression begins when its repressor decays. Theory shows that repressor-decay timers are more robust to parameter variations than activator-relay timers. This motivated us to experimentally compare the relative importance of the relay and decay interactions in-vivo. Comparing WT and mutant NBs at high temporal resolution, we show that the TTF sequence progresses primarily by repressor-decay. We suggest that need for robust performance shapes the evolutionary-selected designs of biological circuits.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
Howard Hughes Medical Institute
- Chris Q Doe
National Institutes of Health (R01-HD27056)
- Chris Q Doe
ERC
- Naama Barkai
BSF (2017055)
- Chris Q Doe
- Naama Barkai
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Wenying Shou, Fred Hutchinson Cancer Research Center, United States
Version history
- Received: May 28, 2018
- Accepted: December 10, 2018
- Accepted Manuscript published: December 10, 2018 (version 1)
- Version of Record published: December 21, 2018 (version 2)
Copyright
© 2018, Averbukh et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A repressor-decay timer for robust temporal patterning in embryonic Drosophila neuroblast lineages
eLife 7:e38631.
https://doi.org/10.7554/eLife.38631
