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Elife. 2018 Dec 10;7. pii: e38631. doi: 10.7554/eLife.38631.

A repressor-decay timer for robust temporal patterning in embryonic Drosophila neuroblast lineages.

Author information

Department of Molecular Genetics, Weizmann institute of science, Rehovot, Israel.
Institute of Neuroscience, Institute of Molecular Biology, Howard Hughes Medical Institute, University of Oregon, Eugene, United States.
Contributed equally


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.


D. melanogaster; biological timer; computational biology; developmental biology; neuroblast; robustness; systems biology

[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

IA, SL, CD No competing interests declared, NB Reviewing editor, eLife

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