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Analyzing Negative Feedback Using a Synthetic Gene Network Expressed in the Drosophila Melanogaster Embryo

Overview
Journal BMC Syst Biol
Publisher Biomed Central
Specialty Biology
Date 2016 Sep 1
PMID 27576572
Citations 1
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Abstract

Background: A complex network of gene interactions controls gene regulation throughout development and the life of the organisms. Insights can be made into these processes by studying the functional interactions (or "motifs") which make up these networks.

Results: We sought to understand the functionality of one of these network motifs, negative feedback, in a multi-cellular system. This was accomplished using a synthetic network expressed in the Drosophila melanogaster embryo using the yeast proteins Gal4 (a transcriptional activator) and Gal80 (an inhibitor of Gal4 activity). This network is able to produce an attenuation or shuttling phenotype depending on the Gal80/Gal4 ratio. This shuttling behavior was validated by expressing Gal3, which inhibits Gal80, to produce a localized increase in free Gal4 and therefore signaling. Mathematical modeling was used to demonstrate the capacity for negative feedback to produce these varying outputs.

Conclusions: The capacity of a network motif to exhibit different phenotypes due to minor changes to the network in multi-cellular systems was shown. This work demonstrates the importance of studying network motifs in multi-cellular systems.

Citing Articles

Tunable self-cleaving ribozymes for modulating gene expression in eukaryotic systems.

Jacobsen T, Yi G, Al Asafen H, Jermusyk A, Beisel C, Reeves G PLoS One. 2020; 15(4):e0232046.

PMID: 32352996 PMC: 7192461. DOI: 10.1371/journal.pone.0232046.

References
1.
Ochoa-Espinosa A, Yucel G, Kaplan L, Pare A, Pura N, Oberstein A . The role of binding site cluster strength in Bicoid-dependent patterning in Drosophila. Proc Natl Acad Sci U S A. 2005; 102(14):4960-5. PMC: 555997. DOI: 10.1073/pnas.0500373102. View

2.
Smidtas S, Schachter V, Kepes F . The adaptive filter of the yeast galactose pathway. J Theor Biol. 2006; 242(2):372-81. DOI: 10.1016/j.jtbi.2006.03.005. View

3.
Driever W, Nusslein-Volhard C . The bicoid protein determines position in the Drosophila embryo in a concentration-dependent manner. Cell. 1988; 54(1):95-104. DOI: 10.1016/0092-8674(88)90183-3. View

4.
Platt A, Reece R . The yeast galactose genetic switch is mediated by the formation of a Gal4p-Gal80p-Gal3p complex. EMBO J. 1998; 17(14):4086-91. PMC: 1170741. DOI: 10.1093/emboj/17.14.4086. View

5.
Milo R, Itzkovitz S, Kashtan N, Chklovskii D, Alon U . Network motifs: simple building blocks of complex networks. Science. 2002; 298(5594):824-7. DOI: 10.1126/science.298.5594.824. View