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Published January 31, 2012 | Published + Supplemental Material
Journal Article Open

Synthetic in vivo validation of gene network circuitry

Abstract

Embryonic development is controlled by networks of interacting regulatory genes. The individual linkages of gene regulatory networks (GRNs) are customarily validated by functional cis-regulatory analysis, but an additional approach to validation is to rewire GRN circuitry to test experimentally predictions derived from network structure. Here we use this synthetic method to challenge specific predictions of the sea urchin embryo endomesoderm GRN. Expression vectors generated by in vitro recombination of exogenous sequences into BACs were used to cause elements of a nonskeletogenic mesoderm GRN to be deployed in skeletogenic cells and to detect their effects. The result of reengineering the regulatory circuitry in this way was to divert the developmental program of these cells from skeletogenesis to pigment cell formation, confirming a direct prediction of the GRN. In addition, the experiment revealed previously undetected cryptic repression functions.

Additional Information

© 2012 National Academy of Sciences. Contributed by Eric H. Davidson, December 9, 2011 (sent for review September 28, 2011). Published online before print January 11, 2012. This research was supported by National Institutes of Health Grant GM 61005. Author contributions: S.S.D. and E.H.D. designed research; S.S.D. performed research; S.S.D. and E.H.D. analyzed data; and S.S.D. and E.H.D. wrote the paper.

Attached Files

Published - 1548.full.pdf

Published - Damle2012p17123P_Natl_Acad_Sci_Usa.pdf

Supplemental Material - pnas.201119905SI.pdf

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