Biography of BIOGRAPHY

ost snapdragons (Antirrhi- num majus) live in scientific obscurity, taking a humble M place in springtime gardens or bouquets. However, in the 1980s, mo- lecular geneticist Enrico Coen helped to place these lowly plants in the spotlight. His work at the John Innes Center (JIC) in Norwich, U.K., used snapdragons as a model organism for studying plant de- velopment. Coen has identified and cloned several genes that affect flower shape, size, and color (1). Using these snapdragon studies and parallel research on Arabidopsis, he and his colleagues developed a unified model to describe how genes interact to direct flower for- mation (2–5). These contributions have earned him numerous awards and recog- Enrico Coen (left) and his collaborator, Przemyslaw Prusinkiewicz, seated on a glacier in Calgary, Canada. nition, such as a 1998 election to the Royal Society in Britain and a 2001 sons. ‘‘I found out that the lec- pursue a less-developed area of re- election as a foreign associate of the

tures began at half-past nine in the search. He concentrated his efforts on BIOLOGY National Academy of Sciences. morning, whereas the chemistry lectures studying the mechanism of ‘‘super In Coen’s most recent work, he has DEVELOPMENTAL began at nine. Also, the genetics people strived to understand how patterns of genes,’’ putative gene clusters that act gave you coffee with your exam, so I gene activity lead to specific sizes and together in ways that affect both evolu- thought they were obviously more civi- shapes of plant organs, a feat that com- tion and development. At the time, one lized,’’ he said. bines experimental studies and com- of the best-defined super genes was in Thus began his career in genetics. puter modeling. In his Inaugural Article, primroses, yet few researchers had Comfortable at the lab where he had published in this issue of PNAS, Coen delved into the molecular aspects of this spent much of his undergraduate years, and his colleagues describe a combina- system. Coen decided to write a pro- Coen chose to stay at Cambridge after tion of factors integrated into a recently posal for molecular research on prim- graduation in 1979 to pursue his doc- developed model to explain petal devel- rose super genes, and he was soon ac- toral degree. Under the mentorship of opment (6). Similar models could even- cepted as a research fellow in the lab of tually be applied to either plants or plant biologist Dick Flavell at the Plant animals, aiding the search for key devel- Breeding Institute, Cambridge. Coen opmental genes. ‘‘We had lovely fields fondly remembers this project, which involved hours of sitting in sunny fields A Blossoming Career of snapdragons, 99.9% collecting primroses with different al- Coen grew up surrounded by science: leles. However, progress was slow be- his father was a physicist and his mother of which were of no cause of the lack of molecular and ge- was a chemist. Drawn to his family’s ca- netic tools to research this system. reer path, Coen decided to take a some- interest to us.’’ what different route by eschewing the The ABCs of Floral Development physical sciences in favor of the life sci- After a year or so, Coen realized that ences. He cultivated an interest in biol- geneticist , he completed his foray into primrose genetics had per- ogy, stimulated at age 15 by a biochem- his thesis in 1982 on the and haps been rather naı¨ve. ‘‘Even though istry book titled The Chemistry of Life function of genes needed to make ribo- I’d now become quite interested in (7). ‘‘[Reading the book] was a real eye somal RNA (8). By examining fruit plants, I started to realize that maybe opener. All of a sudden, I realized you lines that had been subject to selection I’d bitten off more than I could chew,’’ could make sense of the chemical basis for the number of bristles (sensitive he said. Seeking a different plant system of what was going on in living organ- hairs located on the abdomen), Coen to continue his molecular genetics re- found that an exchange of information isms,’’ he said. search, Coen happened upon an open between ribosomal genes on the X and Biochemistry continued to captivate position at JIC, a facility that had stud- Y chromosomes had been responsible Coen throughout high school and col- ied snapdragon genetics for decades. lege. However, during his third year at for a major change in bristle number The head of the program, a plant biolo- the , he fretted (9). This was one of the first cases to gist named Brian Harrison, was about to over which scientific niche to ultimately define the molecular basis of a response retire and Coen, together with colleague concentrate on. Attracted to more ab- to artificial selection. stract analysis, he narrowed his choices With his Ph.D. completed, Coen to either chemistry or genetics, but chose Cambridge again for his postdoc- This is a Biography of a recently elected member of the changed his mind between the two on toral degree. However, disillusioned National Academy of Sciences to accompany the member’s an almost daily basis. In the end, the tie with some of the competitive politics of Inaugural Article on page 4728. was broken by surprisingly simple rea- mainstream science, Coen decided to © 2004 by The National Academy of Sciences of the USA

www.pnas.org͞cgi͞doi͞10.1073͞pnas.0401746101 PNAS ͉ April 6, 2004 ͉ vol. 101 ͉ no. 14 ͉ 4725–4727 Downloaded by guest on September 27, 2021 Cathie Martin, was hired to carry on rally occurring mutants, Carpenter and Harrison’s studies. Coen had to carefully comb through ‘‘I knew zero about snapdragons,’’ extensive snapdragon plantings, search- said Coen. However, he was aware that ing for anything out of the ordinary. snapdragons have transposons, rare ge- ‘‘We had lovely fields full of flowering netic elements that give rise to several snapdragons, 99.9% of which were of no types of mutations. Researchers have interest to us whatsoever. We were look- long known that transposons, also ing for the rare exceptions,’’ said Coen. known as ‘‘jumping genes,’’ move to dif- Along the radial axis, normal snap- ferent positions in the of a sin- dragon flowers have four types of or- gle cell. Geneticist Barbara McClintock, gans arranged in concentric whorls: se- who won the 1983 Nobel Prize in physi- pals on the outside, then petals, ology or medicine, discovered trans- stamens, and finally carpels inside. posons in corn in the 1940s. At the time Within his first few years at JIC, Coen Coen began working at JIC, most trans- saw flowers with one of three morpho- poson research elsewhere continued Mc- logical mutations, later known as types Antirrhinum flowers of wild-type and organ iden- Clintock’s work on corn. However, Har- A, B, and C. The B type, which Harri- tity mutants. (Courtesy of Enrico Coen.) rison saw definite advantages in using son and Carpenter showed Coen on his snapdragons for genetics. ‘‘Snapdragons original tour of the lab, had sepals in- ence in 1989 and subsequently published are smaller plants, and they are nice and stead of petals and carpels instead of in 1990, explained how the functional easy to grow. You can grow large num- stamens. The A type, which he and Car- loss of any one of these gene classes was bers in a smaller space than corn, which penter identified later, had carpel-like responsible for the mutations he had is a bit of a colossal beast,’’ Coen said. organs instead of sepals in the flower’s observed earlier (2). A few months after Using some of Harrison’s material, col- outermost whorl and stamen-like organs presenting his model, Coen heard a talk laborators Heinz Saedler and Hans instead of petals. The C type mutant by a postdoc in the lab of plant geneti- Sommer at the Max Planck Institute in had a repetition of sepal- or petal-like cist Elliot Meyerowitz of the California Cologne had already cloned several ac- organs, rather than stamens and carpels, Institute of Technology and realized tive snapdragon transposons in the early in its two innermost whorls. Coen was that the model Meyerowitz’s group had 1980s, ushering in the molecular era of puzzled about why these three muta- developed for the flowering plant Arabi- snapdragon research. tions took place, but sensed that they dopsis was strikingly similar (10). Coen Upon Coen’s first visit to JIC, Harri- were related. and Meyerowitz later published a joint son and his research technician, Rose- After a long day looking at snap- paper that reviewed these two models mary Carpenter, showed him their ex- dragon flowers, Coen came to a sudden and discussed the idea that a similar tensive collection of mutant conclusion. ‘‘The idea involved a combi- mechanism underlies flower develop- snapdragons. Although Harrison and nation of gene activities: that by having ment in Antirrhinum and Arabidopsis, Carpenter’s work concentrated mostly certain combinations, you could account which likely diverged from a common on color mutations, such as variegated for the particular organ identities ob- plant ancestor about 100 million years flowers, the pair had several snapdragon served in the mutants,’’ he said. ago (3). The discovery suggested that specimens with mutant bloom morphol- Coen eventually discovered that three ‘‘floral development has some unity and ogies. Coen immediately surmised that classes of genes (A, B, and C), later logic to it as opposed to each species because transposons may sometimes christened ‘‘organ identity genes,’’ having its own collection of mutant land within genes important for floral worked in various combinations to con- forms,’’ said Coen. Isolation of the development, they could give research- trol development of each whorl in wild- genes involved, by the labs of Coen, ers a novel way to isolate and study de- type snapdragons: class A controlled Meyerowitz, and of Zsuzsanna Schwarz- velopmental genes in flowering plants. sepal identity, A and B worked together Sommer and Hans Sommer in Cologne, Together with Carpenter, he began to define petal identity, B and C estab- showed that these similarities also ex- screening snapdragons for developmen- lished stamen identity, and C alone tended to the molecular level (4, 11). tal mutants caused by transposon inser- specified carpel identity. Coen’s simple tions. To locate and classify these natu- model, which he presented at a confer- The Genetics of Geometry In the 1990s, Coen and his colleagues at JIC made great strides in identifying genes controlling several other aspects of snapdragon development, such as flower asymmetry and inflorescence ar- chitecture (12–15). However, he gradu- ally became puzzled by another mystery: how interaction between genes and cells affects the development of organ shapes. For example, how do the five petals of a snapdragon grow to form the flower’s distinctively shaped ‘‘mouth’’? This problem required an understand- ing not only of genetics, but of geom- etry as well. Together with computer scientists knowledgeable in biological The four whorls of a wild-type Antirrhinum flower, seen in radial (Left) and longitudinal (Right) cross development, such as Przemyslaw section. (Courtesy of Enrico Coen; illustration by Nigel Orme.) Prusinkiewicz (pictured above) of the

4726 ͉ www.pnas.org͞cgi͞doi͞10.1073͞pnas.0401746101 Brownlee Downloaded by guest on September 27, 2021 University of Calgary (Canada) and An- genetic forces controlled the resulting that many biological shape changes over BIOGRAPHY drew Bangham of the University of East shape: a signal that promotes growth time could be successfully modeled. Anglia (Norwich, U.K.), Coen’s lab has running from the base to the tip of the Although most of his experience thus spent the last decade developing com- flower, and signals causing different re- far has focused on analyzing plant mor- puter modeling techniques that relate gions of petal tube to grow more than phological development, Coen stresses gene activity to patterns of cell division others. that the basic principles he has learned and growth. Last year, Coen, Bangham, The model described in the Nature from developing plant models could eventually be applied to animals. Thus, and graduate student Anne-Gaelle Rol- paper (16) combined several conceptual land-Lagan published a paper in Nature modeling could help speed the search and experimental approaches that Co- for key developmental genes in any or- on one such model that analyzed snap- en’s group had developed to predict bio- dragon petal growth (16). After geneti- ganism, including humans. This broad logical shape change over time. In his cally marking cells in a young white application keeps him deeply interested Inaugural Article, published on page flower bud so that the cells and their and invested in the outcome of his work. 4728 of this issue of PNAS, Coen and progeny appeared red, Coen’s group ‘‘An apple is very different from a watched the flowers blossom into a his colleagues describe factors taken planet in lots of ways, but at the end of spotted or stripy appearance in adult- into account to create such models, us- the day, the great thing about Newton hood. Although they could not observe ing their snapdragon petal model as a was he realized that apples and planets individual marked cells or control the case study. The article discusses how follow the same laws of gravity. There exact starting location with this tech- certain parameters of cell growth, such will certainly be differences when you’re nique, the researchers were able to as- as rate, preferred direction of growth, dealing with plant and animal develop- certain how the petals grew by analyzing and anisotropy, are affected by various ment, but there will be common princi- ples as well. I’m interested in exploring and comparing thousands of spots on genes and morphogens. By accurately both of those things,’’ he said. mature flowers by using a computer. calculating the complex interplay be- The resulting model suggested that two tween these factors, the authors suggest Christen Brownlee, Science Writer

1. Coen, E. S. (1996) EMBO J. 15, 6777–6788. 7. Rose, S. (1966) The Chemistry of Life (Penguin, 12. Luo, D., Carpenter, R., Vincent, C., Copsey, L. & 2. Carpenter, R. & Coen, E. S. (1990) Genes Dev. 4, Toronto). Coen, E. (1996) Nature 383, 794–799. BIOLOGY

1483–1493. 8. Coen, E. S., Thoday, J. M. & Dover, G. (1982) 13. Luo, D., Carpenter, R., Copsey, L., Vincent, C., DEVELOPMENTAL 3. Coen, E. S. & Meyerowitz, E. M. (1991) Nature Nature 295, 564–568. Clark, J. & Coen, E. (1999) Cell 99, 367–376. 353, 31–35. 9. Coen, E. S. & Dover, G. A. (1983) Cell 33, 14. Bradley, D., Carpenter, R., Copsey, L., Vincent, C., 4. Weigel, D. & Meyerowitz, E. (1994) Cell 78, 203–209. 849–855. Rothstein, S. & Coen, E. (1996) Nature 379, 791–797. 5. Coen, E. (2000) The Art of Genes (Oxford Univ. 10. Bowman, J. L., Smyth, D. R. & Meyerowitz, 15. Coen, E. S., Romero, J. M., Doyle, S., Elliott, R., Press, Oxford). E. M. (1991) Development (Cambridge, U.K.) Murphy, G. & Carpenter, R. (1990) Cell 63, 1311– 6. Coen, E., Rolland-Lagan, A.-G., Matthews, M., 112, 1–20. 1322. Bangham, A. & Prusinkiewicz, P. (2004) Proc. 11. Schwarz-Sommer, Z., Davies, B. & Hudson, A. 16. Rolland-Lagan, A.-G., Bangham, J. A & Coen, E. Natl. Acad. Sci. USA 101, 4728–4735. (2003) Nat. Rev. Genet. 4, 655–664. (2003) Nature 422, 161–163.

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