A two-headed Xenopus embryo formed in response to inappropriate activation of the Wnt signalling pathway.

Introduction

The different cell types of the body are formed in the right place and at the right time in response to signals that are produced by special organiser regions of the embryo.

Cells developing in a zebrafish embryo.

Figure 1. Use of bimolecular fluorescence complementation reveals that signalling by nodal family members is strong near the margin of the zebrafish embryo (bottom of image) and weak near the animal pole (top).

These so-called morphogens act in a concentration-dependent manner to induce the formation of different cell types at different positions within developing tissues. One of the earliest interactions of this kind is mesoderm induction, which results in the formation of organs and cell types such as heart, muscle, kidney and bone.

We use frog, zebrafish and mouse embryos to study mesoderm-inducing factors and to ask how cells respond to them. One aim is to understand how the signals exert long-range effects in the embryo, and how cells distinguish between different morphogen concentrations to activate different genes. We go on to explore how these different genes then participate in the genetic regulatory networks that result in the formation of specific cell types. The principles we define in the early embryo inform additional work on events in later development, including the heart and vasculature. They are also relevant to work on embryonic stem cells, where we hope that our experiments will help direct ES cells down particular developmental pathways.

Selected publications