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Insight into the genetic pathways that drive segmentation like clockwork

Kansas City, Mo. - Researchers at the Stowers Institute for Medical Research are gaining new insight into the molecular players involved in the process of vertebral column formation in the embryo.

A research team headed by Dr. Olivier Pourquie, currently an Associate Scientist at the Stowers Institute, were pioneers in providing evidence for an oscillator called the segmentation clock, a timing mechanism responsible for the periodic production of the somites (the precursors of the vertebrae) in the embryo. This group now reports that the Notch signaling pathway provides the backbone of the segmentation clock in the chick embryo. These findings are reported in the Jan. 12 Advance Online Publication of the journal Nature at http://www.nature.com by Dr. Pourquie and co-authors Drs. Kim Dale and Miguel Maroto, senior research associates of Dr. Pourquie and co-equal contributors to the research. The paper's title is "Periodic Notch inhibition by lunatic fringe underlies the chick segmentation clock."

The group discovered that one of the genes controlled by the segmentation clock, lunatic fringe , is involved in a negative feedback loop resulting in the periodic inhibition of Notch signaling. Abnormalities in this signaling loop in mice and humans can lead to severe defects in vertebral column formation and can also be linked to the development of other more widespread pathological conditions of the vertebral column such as scoliosis.

Robb Krumlauf, Scientific Director of the Stowers Institute, said, "These results are very exciting and important because components of the Notch pathway, such as Jagged, Delta 3 and Lunatic fringe have been previously associated with vertebral defects in mouse models and in human syndromes. However, the basis of these skeletal defects was previously unknown, and this discovery firmly links the problems to early patterning processes regulated by the
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Contact: Laurie Wimberly
llw@stowers-institute.org
816-926-4015
Stowers Institute for Medical Research
12-Jan-2003


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