USC Scientists Uncover Secrets Of Feather Formation; "Jurassic Chicken" Project May Help Studies Of Human Development And Evolution Of Dinosaurs

A paper describing this work, "The Morphogenesis of Feathers", authored by principal investigator and Keck School pathology professor Cheng-Ming Chuong and his colleagues, was selected for advance online publication in the journal Nature and will be available as of October 30, 2002.

"The feather is one of the best research models you can find for understanding the basic molecular pathways used by all epithelial cells," says Chuong. "Scientists agree that whether you're looking at a human mammary gland or a chicken feather, epithelial cells use the same underlying logic, the same grammar, to form an organ. But unlike a gland, a feather really lays everything right out there for you."

The question of what makes a feather a feather has become rather heated in the recent past, with the discovery in China in the 1990s of fossilized dinosaurs like the Sinorthosaurus (Chinese-bird-dinosaur), with branching skin appendages on its skin. "Some say these things are feathers, some say they're protofeathers, others say they're not feathers at all," Chuong explains. "Everybody wants to know which one is the real first feather."

And they want to know how it came to be, as well. Over the years, Chuong notes, paleontologists trying to trace the evolutionary connection between dinosaurs and birds have looked at the ways in which a reptilian scale might turn into an avian feather.

Most adult feathers have a backbone, or stem, called a rachis, off of which the feather's barbs branch; each individual barb then branches again into the feather's smallest unit, the barbule, which is made of a single row of epithelial cells. Downy feathers, like those on a chick, lack a rachis altogether and are made up of just barbs studded with barbules. The standing hypothesis among many paleontologists has long been that the scales on dinosaurs must have lengthened into rachides that then became notched to form barbs and barbules. But there has been no real molecular evidence to either back up or refute that argument. Until now.

In their Nature paper, Chuong and his colleagues have demonstrated just how barbs and rachides are formed in a modern chicken, and have at the same time demonstrated that the evolution from scale to feather most likely followed a path in which the barbs form first and fuse to form a rachis-rather than a rachis forming first, and then being sculpted into barbs and barbules. This interaction between evolutionary biology and developmental biology (dubbed Evo-Devo) is a relatively new marriage of two previously disparate fields.

To come to their conclusions, Mingke Yu, the postdoctoral fellow and first author on the paper, along with colleagues Ping Wu and Randall B. Widelitz in Chuong's laboratory, developed a novel way to genetically manipulate different genes during feather formation. They plucked feathers from chickens, then prompted the chicken to regenerate those feathers under controlled conditions, raising and lowering the expression levels of the genes in question on an individual basis and observing the effects they had on the organization of epithelial cells into different feather forms.

Among others, three genes in particular-noggin, bone morphogenetic protein 4 (BMP4), and the whimsically named sonic hedgehog (Shh)-were found to result in new feathers that were rife with abnormal organization in their rachides and barbs. When Chuong's team increased the expression of noggin, for instance, they found that the rachis began to split into several small, thin rachides, and the barbs increased in number. When they increased the expression of BMP4, with which noggin interacts antagonistically, they found that the feather's rachis became gigantic and its barbs merged and were reduced in numbers. In this way, they were able to essentially manipulate the number and size of the feather's barbs and rachides.

Finally, when they suppressed Shh, they found a residual webby membrane between the normally separated barbs. "The cells there were supposed to go through apoptosis, or cell death," says Chuong, "in order to create the space between the barbs. But when we took away the sonic hedgehog signal, cell death no longer occurred. It is a similar process to that which occurs in the web of duck feet."

What can these new findings on the morphogenesis of feathers tell us about their evolution? "These results suggest that the barbs form first and later fuse to form a rachis, much like downy feathers are formed before flight feathers when a chicken grows up. Under the general rule of ontogeny repeating phylogeny, downy feather made only of barbs probably appeared before the evolution of feathers with rachides and capable of flight," Chuong says. "However, pinning down the exact moment at which dinosaur scales become chicken feathers is non-realistic. Just like Rome, feathers are not made in one process. It took 50 million years for Nature to refine the process, to transform a scale into a flight machine. There were many, many intermediate stages.

"While Darwin's theory has explained the 'why' of evolution, much of the 'how' remains to be learned," Chuong adds. "Evo-Devo research promises a new level of understanding."

These findings also have medical applications, notes Chuong. "With this study, we learned more about how nature guides epithelial stem cells to form different organs. For example, BMP, Shh and noggin are also used in different ways in making lungs, limbs and spinal cords. By analyzing these models, scientists may be able to fully understand nature's 'grammar,' and learn to use it in repairing or regenerating tissues and organs, which we call tissue engineering."

This research was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health, and from the National Science Foundation.

Mingke Yu, Ping Wu, Randall B. Widelitz and Cheng-Ming Chuong, _The Morphogenesis of Feathers._ Nature advance online publication, 30 October 2002 (doi:10.1038/nature01196).