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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