Dr Henrietta J. Standley - PhD
Mechanisms of cell commitment in Xenopus laevis
eFGF-treated cells are able to express muscle-specific genes in the absence of cell contact, visualized here with an antibody against the transcription factor XMyoD, suggesting that eFGF can behave as a myogenic community factor.
I am particularly interested in understanding the mechanisms by which a combination of inherited factors and intercellular signals cause a cell to become committed to a particular fate. I have focused on the community effect and axis formation in development of Xenopus laevis embryos, which are especially amenable to micromanipulation.
The community effect describes a signalling interaction within group of cells that is essential for them to be able to differentiate. One such interaction takes place within the group of muscle precursor cells found in the dorsolateral mesoderm of the early gastrula embryo. During my Ph.D. with Prof. Sir John Gurdon at the University of Cambridge I used a candidate approach to identify the community factor responsible for mediating this interaction. I determined that eFGF behaves as the endogenous myogenic community factor. More recently I have used single cell transplantations to investigate when cells of the vegetal hemisphere become determined to contribute to the endoderm germ layer, where they will give rise to the intestines and associated organs.
Embryos derived from oocytes depleted of maternal pygopus mRNA (bottom) have a ventralised phenotype, indicating that pygopus is required for development of the dorsal structures present in the normal embryo (top).
The dorsoventral axis of the developing Xenopus embryo is established by activation of the Wnt/ beta-catenin pathway. The components of this pathway are synthesised maternally and are present in the Xenopus oocyte before fertilisation. While in Prof. Janet Heasman’s laboratory at the Cincinnati Children’s Hospital Research Foundation, I used antisense methods to deplete oocytes of maternal mRNAs encoding various members of the Wnt pathway. I then analysed the phenotypes of embryos developing from these depleted oocytes to determine the contribution of each factor to normal development. I found that the beta-catenin interacting proteins XTcf1, XTcf4, and pygopus have distinct and required roles in establishing the dorsoventral axis.