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Citation
Cassidy, J.J., Bernasek, S.M., Bakker, R., Giri, R., Peláez, N., Eder, B., Bobrowska, A., Bagheri, N., Nunes Amaral, L.A., Carthew, R.W. (2019). Repressive Gene Regulation Synchronizes Development with Cellular Metabolism.  Cell 178(4): 980--992.e17.
FlyBase ID
FBrf0243125
Publication Type
Research paper
Abstract

Metabolic conditions affect the developmental tempo of animals. Developmental gene regulatory networks (GRNs) must therefore synchronize their dynamics with a variable timescale. We find that layered repression of genes couples GRN output with variable metabolism. When repressors of transcription or mRNA and protein stability are lost, fewer errors in Drosophila development occur when metabolism is lowered. We demonstrate the universality of this phenomenon by eliminating the entire microRNA family of repressors and find that development to maturity can be largely rescued when metabolism is reduced. Using a mathematical model that replicates GRN dynamics, we find that lowering metabolism suppresses the emergence of developmental errors by curtailing the influence of auxiliary repressors on GRN output. We experimentally show that gene expression dynamics are less affected by loss of repressors when metabolism is reduced. Thus, layered repression provides robustness through error suppression and may provide an evolutionary route to a shorter reproductive cycle.

PubMed ID
PubMed Central ID
PMC6865806 (PMC) (EuropePMC)
Related Publication(s)
Note

Slow Down to Catch Up.
Jagannathan et al., 2019, Cell 178(4): 774--776 [FBrf0243197]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Cell
    Title
    Cell
    Publication Year
    1974-
    ISBN/ISSN
    0092-8674
    Data From Reference