Vol 461 | Issue no. 7260 | 3 September 2009 AUTHORS

Abstractions MAKING THE PAPER LAST AUTHOR Bess Ward Despite numerous medical advances, heart disease remains a dominant cause loss in the is a of death worldwide. Many genuine puzzle still to be solved. fish and amphibians can regenerate and repair Why are some areas of the world’s oceans rich damaged heart tissue; in plant growth, whereas others are biologi- humans, unfortunately, cannot. However, cal deserts? The answer is that more than half work by Benoit Bruneau at the Gladstone the has too little nitrogen to support the Institute of Cardiovascular Disease in San growth of microscopic plants, or phytoplank- Francisco, California, and his colleagues has ton. But where does the missing nitrogen go? European investigators had devised new meth- thrown light on the little-understood topic For decades most oceanographers, includ- ods for measuring and denitrifica- of mammalian and reptilian heart evolution. ing Bess Ward at in New tion in small (10 millilitre) samples of ocean Two findings, which centre on how the protein Tbx5 regulates the growth of a subset of heart Jersey, thought ‘’ was responsi- water. “The methods were so new and so dif- cells, may lead to new treatments for human ble for virtually all nitrogen loss in the ocean. ferent that a lot of people were suspicious there heart disease. The first revelation was that In oxygen-poor areas of the ocean, anaero- might be some artefact involved,” says Ward. this protein, along with two others, could be bic , which do not rely on oxygen for “So Jeremy visited some of our European col- manipulated to induce embryonic mouse cells their growth, use biologically available forms leagues and learned the methods, so we could to develop into cardiac cells (J. K. Takeuchi and of nitrogen, such as nitrates and nitrites, for go out and try to reproduce their results.” Ward B. G. Bruneau Nature 459, 708–711; 2009). energy generation, producing, through several and her colleagues also developed their own Now, Bruneau and his team show that, in intermediate steps, dinitrogen (N2) — a form methods for measuring denitrification and two reptiles, Tbx5 is a key determinant in the of nitrogen that plants cannot use. anammox in larger (10 litre) samples. heart’s division into two chambers — and that, But starting in 1995, investigators in the The next step was to apply the techniques in mice, the protein’s absence has a drastic Netherlands, Germany and Denmark uncov- to different parts of the ocean. First stop was effect on heart structure (see page 95). ered an additional biochemical reaction, called Chesapeake Bay, on the east of the United anaerobic ammonia oxidation, or anammox, States, where Ward’s team found “exactly what You began by studying mouse heart-cell that produces N2 in ocean waters. Here, the we expected in our own backyard, which was growth, then moved on to reptilian hearts. − bacteria responsible use up nitrite (NO2 ) and both anammox and denitrification” occurring Why the interest in different organisms? + ammonia (NH4 ) to directly generate N2. together, she says. In the Eastern Tropical South By comparing different organisms, we can The Europeans showed that anammox, in the Pacific, however, off the coast of Peru, “we got often gain insight into similar processes. To absence of denitrification, accounted for most, if exactly what the Europeans had, which was all try to understand the function of Tbx5 in not all, N generation. “But given the chemistry anammox and no denitrification”, she says. Con- heart disease, we deleted the Tbx5 gene from 2 of the two processes it was impossible for us to vinced that their methods were working, Ward specific chambers of the heart, essentially turning the mouse heart into what looked like understand how that could be,” says Ward. and her colleagues made an additional stop in a frog heart. We then studied reptilian hearts The problem, she thought, was that nitrite the Arabian Sea, “where it turned out that it was to look into the patterned expression of Tbx5 and ammonium are intermediate products in all denitrification and very little anammox” and gain a broader perspective on the gene’s the denitrification process. And in oxygen-poor (page 78). role. We didn’t know how important Tbx5 waters, denitrification is the only substantial So in different parts of the ocean, and at might be in cardiac chamber formation, or in source of these chemicals. “We couldn’t under- different times, a variety of mechanisms may its evolution. stand how anammox could be occurring in the be responsible for marine nitrogen loss. “We absence of denitrification,” says Ward, “so that’s used to think we understood denitrification What was the hardest part of the work? what we set out to resolve.” and now we know we don’t,” says Ward. The Locating literature on reptilian heart This involved sending postdoc Jeremy Rich, current study “does not increase clarity”, she development. The newest paper I could now a researcher at Brown University in Provi- says. “But it makes it more compelling that we find that described the embryology was a dence, Rhode Island, on a trip to Europe. The find the answer.” ■ German monograph from 1903. Some of its predictions were right on the money, but there were dissenting responses from others also studying the reptile heart. Reptiles have FROM THE BLOGOSPHERE a broad spectrum of morphology, and no If you weren’t one of the 200 The film shows just how an co-founder of DIYbio.org, an one could make head nor tail of their hearts. or so people invited to Science ‘unconference’ runs — with online community for amateur People offered differing interpretations of the Foo Camp this year, you can attendees rushing to scribble scientists. same morphology in their own papers. experience a snippet of the down their own agenda on the Tim O’Reilly, chief executive “gathering of geeks” that took first day. Talks such as “Can of O’Reilly Media and after Is your work important to human health? Now that we understand how important Tbx5 place earlier this summer biology help us understand whom Foo is named (friends of is to ventricular separation, we can focus at Google’s headquarters in the financial crisis?” and “Is O’Reilly), points out, “If you had on how it helps the heart develop a septum. Mountain View, California. ‘evil’ in our brains and can a bunch of really smart people Human Tbx5 mutations cause septation A video produced by Nature we control it?” peppered the over to your house, would defects, which are very common in children podcast producer Charlotte whiteboard. The gathering you think you had to have a with congenital heart disease. Understanding Stoddart has been posted on included people such as the programme? Of course they’re the role of Tbx5 in building and separating the The Great Beyond blog (http:// mathematician who designed going to find things to talk heart into ventricles will probably be broadly tinyurl.com/mfe4g4). a non-reversing mirror and the about!” ■ applicable to understanding and treating Visit Nautilus for regular news relevant to Nature authors ➧ http://blogs.nature.com/nautilus and see heart diseases caused by genetic defects. ■ Peer-to-Peer for news for peer reviewers and about peer review ➧ http://blogs.nature.com/peer-to-peer.

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