Modeling oscillatory gene expressions in the Wnt and Notch – Niels Bohr Institute - University of Copenhagen

Niels Bohr Institute > Calendar > 2008 > Modeling oscillatory g...

Modeling oscillatory gene expressions in the Wnt and Notch

Somites are aggregations of cells appearing along the future vertebral column during the early development of all vertebrates. As the precursors of much of the axial skeleton, the process of somitogenesis is a pivotal event in vertebrate embryology. Somites form periodically, which suggests the involvement of a cellular clock, the so-called segmentation clock. Several target genes of the Wnt and Notch signaling pathways are known to be involved in somitogenesis, and display oscillatory expression patterns. The segmentation clock is thought to operate via negative feedback loops between these species. Interestingly Wnt and Notch target genes oscillate out of phase.

I propose a novel intracellular oscillator in the canonical Wnt pathway. The model is based on a negative feedback loop involving Axin2 and the destruction complex, and implements the saturated degradation of Axin2. The model is capable of producing sustained oscillations with periods matching the segmentation clock. Through the suggested crosstalk candidate GSK3β, this oscillator is coupled to the lunatic fringe and Hes7 feedback loops of the Notch pathway. The combined system exhibits coupled oscillations with phaseshift.

Supervisors: Mogens Høgh Jensen (NBI) & Axel Hunding (Kemisk institut)

There will be a small reception after the talk, in the common room on the B-floor in building K