nice to read a perspective in @genesdev.bsky.social on our recent paper genesdev.cshlp.org/content/earl...

More to come soon, both in continuing to examine the genomic regulation, but also defining the cellular behaviors that are necessary for early heart tube formation. For now, huge thanks to @benoitbruneau.bsky.social for supporting me as we pursued this ambitious and open-ended project!
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In what @benoitbruneau.bsky.social aptly described as our “lets go nuts” experiment, we confirmed this interaction by demonstrating that reduced Nr2f2 dosage partially rescues the Mef2c KO heart tube phenotype.
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Finally, Alex Clark and @jsauce7.bsky.social helped us construct gene regulatory networks for each of the outflow tract, ventricle, and inflow tract segments of the heart tube. Using these networks, we identified a previously unknown genetic interaction between Nr2f2 and Mef2c.
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By collaborating with @tanvis.bsky.social and Brian Black at UCSF, we showed via zebrafish transgenesis that many of our predicted elements exhibited clear enhancer activity in the developing heart.
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We hypothesized that MEF2C acts via segment-specific enhancers to drive distinct patterns of gene expression in the early heart and used our multiomics datasets to predict such candidate enhancers.
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We found that loss of MEF2C causes a broad “posteriorization” of the early heart tube. In both gene expression and chromatin accessibility modalities there were some changes that were universal throughout the heart tube, and others that were specific to distinct segments of the tube.
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Loss of the transcription factor MEF2C leads to embryonic lethal defects in early heart development. In this paper, we used multiomics (snRNA- and snATAC-seq) to understand precisely what goes wrong when MEF2C is absent.
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