University of Dundee

‘Molecular clock’ deciphered by Dale Lab collaboration

07 Sep 2015

Temporal control of a ‘molecular clock’ that plays a vital role in the embryonic development of the skeleton and skeletal musculature has been deciphered for the first time by researchers at the University of Dundee.
Understanding the segmentation clock mechanism will aid in the identification of protective factors for normal spinal development ultimately creating a better understanding of ways to prevent and better treat various spinal conditions.
The research has been led by Dr Kim Dale in the School of Life Sciences at Dundee in an inter-disciplinary collaboration with Dr Philip Murray from the University’s Mathematics department. The resulting paper has been published in the eLife journal.
Dr Dale explained, “Early in vertebrate embryogenesis, embryos generate transient structures called somites which give rise to the vertebrae of the skeleton and the skeletal musculature.
“Interference with somitogenesis can lead to severe segmentation and skeletal defects. The time taken to form each somite is tightly regulated and is a defining characteristic of each vertebrate species. It is regulated by a molecular clock that has been the focus of a huge amount of investigation over the last 15 years.
“This clock determines the size and number of segments formed in the developing skeleton but the principles underlying this periodicity are still not fully understood. We show for the first time that the stability and turnover of NICD, a key Notch signalling component, is inextricably linked to the regulation of the pace of the clock. Our results provide a novel and important insight into the mechanism underlying the segmentation clock.
“This study has been a close cross-disciplinary collaboration with Dr Philip Murray. The development of a mathematical model helped us to formulate and test hypotheses and relate observations made at different scales. The interdisciplinary approach has allowed the lab to follow  exciting new avenues and directions.”