Aulehla Group
Timing of mammalian embryogenesis
In situ hybridisation of mouse embryo at day 9 of development. Uncx4.1 mRNA is visualized in formed somites, while Wnt3a mRNA is expressed in the posterior embryo.
A: Data from two-photon real-time imaging experiments performed in a transgenic reporter mouse embryo. The fluorescence reflects transcriptional activity of the lunatic fringe gene. Note dynamic changes of fluorescence in tail part of embryo (white box). B: Quantification of fluorescent signal within the tail region (white box in A) identifies striking oscillations.
Previous and current research
During an embryo’s journey from a single cell to a complex organism, countless patterning processes unfold with remarkable precision, both spatially but also in respect to their temporal sequence, or timing. This temporal aspect of embryonic development is the focus of our research. How is time measured during embryonic development and what extrinsic and intrinsic signals control this timing? How do embryonic clocks function? We aim to approach these questions by studying the mechanisms controlling overall developmental rate, as well as by studying the timing of individual processes, including the dynamics of underlying signalling pathways.
One such embryonic clock, the somite segmentation clock, is thought to control the formation of the pre-vertebrae that form periodically in a head-to-tail sequence within the paraxial mesoderm, with a periodicity around two hours. In mouse embryos this clock drives the oscillatory activity of several signalling pathways (Wnt, Notch and Fgf signalling) in the forming mesoderm. How these oscillations are generated in the first place and what ultimately controls and tunes the periodicity of these oscillations is unknown. To address these questions, the ability to directly observe and quantify the temporal dynamics of signalling pathway activity is a key prerequisite.
We have been able to visualise oscillatory transcriptional activity in developing mouse embryos with high temporal and spatial resolution. We are now developing this approach further and are establishing a novel and versatile real-time reporter system that will allow us to visualise the dynamics of Wnt-signalling activity at various levels. This signalling pathway serves a multitude of evolutionary conserved functions during development and has been shown to play an essential role during somite formation. The real-time reporter system is designed to refl ect Wnt-signalling activity both at transcriptional as well as translational level, directly in the context of developing mouse embryos. This will enable us to determine how the striking oscillations of Wnt- signalling activity are generated and to functionally test their role in embryonic patterning. We are particularly interested in identifying the intrinsic and extrinsic factors that are responsible for controlling these oscillations within the segmentation process. The insight gained from studying this specific oscillation phenomenon will be combined with our efforts that address the mechanisms that control the overall timing of development.
Future projects and goals
Using a combination of classical experimental embryology, mouse genetics, EScell technology and our expertise in real-time imaging of mouse embryos, our future goals are:
- Identification of extrinsic and intrinsic signals controlling the timing of mouse development;
- generation of a real-time imaging reporter system for Wnt-signalling oscillations in mouse embryos using embryonic stem cell technology;
- analysis of the mechanisms underlying Wnt-signalling oscillations during embryogenesis;
- discovery of novel oscillatory phenomena during embryogenesis.