Role Of Growth Factor In Vertebrae Formation Demonstrated

The Pourquié Lab has long studied the formation of vertebrae, and the lab team has made significant contributions to the currently accepted "clock and wavefront" explanation of somitogenesis. The theory suggests that a periodic mechanism -- the segmentation clock oscillator -- interacts with a molecular "wavefront" of differentiation, converts information from the clock into positional information, and allows for the formation of vertebrae precursors known as somites.

In this paper, the team successfully characterized and verified the proposed role of FGF signaling during somitogenesis using a mouse lacking the FGF receptor Fgfr1. They also published two important secondary findings related to FGF signaling:

1) FGF controls the clock, since the cyclic genes of all pathways (WNT, NOTCH, and FGF) eventually lose their dynamic expression; and

2) by pharmacological inhibition of FGF signaling, they identified a signaling hierarchy controlling clock oscillations downstream of FGF signaling.

"These findings show that both signaling pathways implicated in setting the wavefront, FGF and WNT, are also necessary for the function of the segmentation clock," said Matthias Wahl, Ph.D., Postdoctoral Research Associate and first author on the paper. "This understanding opens the door to exciting new projects. Thanks to the characterization of the Fgfr1 mouse mutant, we will be able to generate genetic crosses with null mutants for other signaling pathways involved in somitogenesis and characterize genetically the interplay between the signaling pathways."

"A number of genetic diseases, including congenital scoliosis, result from problems in somitogenesis and segmentation during embryogenesis," said Olivier Pourquié, Ph.D., Investigator and senior author on the paper. "We believe that any new insight into the process of somitogenesis will improve understanding of the disease process and may eventually lead to a treatment for these devastating diseases. We are excited to continue studying these pathways and their implications on somitogenesis."

Additional contributing authors include Chuxia Deng, Ph.D, Genetics of Development and Diseases Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; and Mark Lewandoski, Ph.D., Laboratory of Cancer and Developmental Biology, National Cancer Institute-Frederick.

*The paper will appear in the November print issue of the journal.