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ECB-ART-42297
Proc Natl Acad Sci U S A 2012 Jan 31;1095:1548-53. doi: 10.1073/pnas.1119905109.
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Synthetic in vivo validation of gene network circuitry.

Damle SS , Davidson EH .


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.

PubMed ID: 22238426
PMC ID: PMC3277137
Article link: Proc Natl Acad Sci U S A
Grant support: [+]

Genes referenced: LOC100887844 LOC115919910 LOC575170 LOC582915

References [+] :
Akiyama, The gcm-motif: a novel DNA-binding motif conserved in Drosophila and mammals. 1996, Pubmed