The birth of a beak

USC researchers detail process of beak formation in journal Science

The shapes of avian beaks are determined by areas of active growth amidst areas of slow growth in a developing embryo, and are associated with activity levels of a specific protein called bone morphogenetic protein 4 (BMP4), according to a group of researchers from the Keck School of Medicine of the University of Southern California. Their paper, which describes this molecular beak-shaping process, will be published in this week’s issue of the journal Science. A report on this paper and another closely related study will appear in the journal’s news section.

Different bird species tend to have differently shaped beaks, which are said to reflect the different evolutionary pressures under which they develop. In fact, Charles Darwin looked to 13 different species of finch from the Galapagos Islands to help bolster his theories of evolution, showing that while the Galapagos finches had most likely descended from a common ancestor, they had developed into distinct species based on differences in their beaks-differences which corresponded with their confinement to different islands in the archipelago and their adaptation to different ecological niches.

Today, beak shape is considered “a classical example of evolutionary diversification,” writes Cheng-Ming Chuong, M.D., Ph.D., principal investigator on the Science paper and professor of pathology at the Keck School of Medicine, along with his colleagues. Still, while the reason for this diversity is explained by evolutionary selection, little is known about how different beak shapes are built at the cellular and molecular level. “Since beaks are made from cells, each ’designer beak’ must be made through differences in the regulation of cell behaviors,” Chuong notes.

Beaks are actually a collection of “facial prominences,” says Chuong, and these prominences grow at varying rates during chick development to “compose a unique beak.” But while early chicken beak development has been studied to some degree, little is known about how these shapes are created in the later stages of development.

To shed some light on that question, Chuong and colleagues compared beak development in chickens and ducks: Duck beaks are long and wide, Chuong notes, while chicken beaks are small and have a conical shape. In their studies, the researchers focused on one particular facial prominence called the frontonasal mass, or FNM.

Research associate Ping Wu, Ph.D., the paper’s first author, found that in chickens and ducks there are two areas in the developing FNM in which cells divide rapidly to create the beak’s mass. In chickens, these two areas gradually converge into one area on the distal end of the beak, creating a sharp, growing tip. In ducks, two such proliferative zones remain, creating a wider, bigger beak.

Using in situ hybridization techniques, the researchers tracked the levels of a number of growth-related genes. They were able to pinpoint BMP4 as a candidate for mediating growth, Chuong says. In humans, several BMPs play a role in enhancing the rates of cell division and growth and regulating major developmental events including bone differentiation. Deregulation of BMP pathway activity has also been linked to some tumor growth.

To test whether or not BMP4 is indeed a growth mediator, they used techniques from gene therapy and protein delivery to mis-express BMP4 and its antagonist. “The results,” Chuong says, “were astounding. The chicken beaks were modulated into a spectrum of beak shapes mimicking those seen in nature.”

An accompanying paper in Science, which looked at molecular differences among the Galapagos finches themselves, also identified BMP4 as a major mediator of beak shape in a variety of finch species.

Together, these two studies are able to point to BMP4 as having a major role in the creation of the avian beak, demonstrating that it is “one of the major driving forces building beak mass.” “By ’tinkering’ with BMP4 in beak prominences,” Chuong and his scientific colleagues write, “the shapes of the chicken beak can be modulated.” “These two papers in Science represent a a major step in basic biology,” Chuong says, “moving toward a molecular understanding of Darwin’s evolutionary theories. The principals learned here also have practical implications. Learning how nature ’engineers’ stem cells and molds them into specific organs will help scientists make progress in tissue engineering.”

The next step, says Chuong, is to look into how these areas of cell proliferation are localized physiologically, “an issue that’s also of concern to cancer research,” he adds. In addition, he and his colleagues will be trying to understand how BMP4 and other morphogenetic molecular activities are regulated to adapt to environmental changes.

Chuong’s laboratory has taken a global approach to the study of how organs of different structures, sizes and shapes are produced in evolution and development. Their earlier work on the 120-million-year-old Longirostravis, the earliest wading bird, prompted them to begin looking further into the molecular bases of beak shape and chicken teeth in evolution.