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Ozbudak Lab Published Third Paper This Year
During the patterning of the vertebrate anterior-posterior axis, a gene expression oscillator controls segmentation of the somites, the precursors of the vertebral column. Several mathematical models have been developed to explain how this segmentation clock works. Now, Stephan Knierer, Ertugrul Özbudak and their collaborators developed a multicellular stochastic computational model of the zebrafish segmentation clock. Simulations run with this model show that autoregulatory negative feedback loops of dimers of Hairy/enhancer-of-split-related (Hes/Her) proteins -- transcriptional repressors that are encoded by the only known conserved vertebrate oscillating genes -- can drive synchronized gene expression oscillations in wild-type zebrafish embryos and can recapitulate various mutant phenotypes. The model also predicts that synchronized oscillations can only be generated if zebrafish Her proteins have a half life of less than 6 minutes, a prediction that the researchers validate by showing that Her7 has a half life of 3.5 minutes. Importantly, this model can now be used to make predictions for future experimental studies.
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