Q: Magazine Issue 5 Feb. 2021 Feb. 2021 | Page 9

That evolution has led to a diverse array of research pursuits . Like one that involves an entirely different kind of evolution : our shared ancestry with fish .
GLOWING HEARTS
Several floors down , the team of molecular biologist Christian Mosimann , PhD , is injecting DNA into the embryos of zebrafish . The DNA will make them glow in the dark .
“ They tolerate it really well ,” he says . “ I don ’ t think they know they ’ re glowing .”
Fish , like all vertebrates , have a lot of genetic material in common with humans , and their cardiovascular systems work in much the same way , with a centralized heart that pumps blood to deliver oxygen and other nutrients through the body .
Dr . Mosimann and his research group are interested in how that system develops .
“ Through genome sequencing , we can pinpoint the changes patients with cardiovascular anomalies have in their genome ,” he says . “ And with CRISPR technology we can then introduce those mutations in zebrafish and see , in great detail , what effect these changes have on cardiovascular development .”
That ’ s possible through Dr . Mosimann and his lab ’ s work uncovering the first genetic means to track the lateral plate mesoderm , or
LPM ( 2 ), the group of cells that go on to build the heart and its associated organs .
“ These systems reflect what heart and circulatory systems looked like millions of years ago , when we were not even fish yet ,” says Dr . Mosimann , “ but something much more primitive .”
Having identified the proteins that regulate the LPM ’ s emergence in the embryo ( 3 ), Dr . Mosimann ’ s lab can label the earliest heartforming cells with transgenic markers that color-code their parts . It works in several different animal models , but it ’ s especially useful in zebrafish , because you can see right through them .
The discoveries are intriguing . LPM cells go on not only to build the heart and circulatory system , but also to build disparate systems further flung : bones in the upper extremities , muscles in the neck and face . That insight has put previously clinical diagnoses like Halt-Oram syndrome , characterized by heart problems and anomalies in the hands , in new context . Both heart and hand issues are linked in early development and correlate with a mutation of the gene TBX5 . Indeed : TBX5 mutations in zebrafish result in heart problems and missing pectoral fins .
“ That ’ s the big picture ,” says Dr . Mosimann . “ If we can model complex , connected heart disease in fish and learn what phenotypes we need to pay attention to , then maybe eventually we can say , ‘ Well , the patient has this mutation ; fish with the same mutation
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“ These systems reflect what heart and circulatory systems looked like millions of years ago , when we were not even fish yet ,” says Dr . Mosimann , “ but something much more primitive .” Photos by Christian Mosimann , PhD
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