Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.659976
Title: A study of the expression and function of differentiation inhibiting activity and its receptor in the early mouse embryo
Author: Nichols, Jennifer
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1994
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Abstract:
In this thesis the maintenance of the pluripotential stem cells of the early mouse embryo is investigated. Differentiation Inhibiting Activity (DIA) is a cytokine able to prevent the differentiation of pluripotential embryonic stem (ES) cells in vitro when added to the medium in picomolar concentrations. In this study the mRNA for DIA and the components of its receptor are shown, by in situ hybridisation, to be present in the murine blastocyst. DIA is expressed primarily in the trophectoderm, the first tissue to differentiate in the embryo, whereas the expression of its receptor is predominantly restricted to the undifferentiated inner cell mass (ICM). This suggests a paracrine interaction between the trophectoderm and the ICM such that the differentiated trophectoderm produces DIA which binds to the receptors on the cells of the ICM to maintain their pluripotential state. The effects of DIA on the developing embryo were investigated using ES cells which had been mutated to produce increased amounts of DIA and injected into blastocysts to generate chimaeras. The resulting abnormal phenotypes are consistent with perturbation of the stem cell pool, and indicate that the cells in the early developing embryo are responsive to DIA. These results are considered in the light of recent findings that homozygous DIA-deficient embryos are capable of development to term, but that homozygous females cannot support implantation. Alternative factors which may play a role in stem cell maintenance have been investigated. Likely candidates are interleukin-6 (IL-6), oncostatin M (OSM) and ciliary neurotrophic factor (CNTF), since, in common with DIA, their receptors utilise the signal transducing subunit gp130.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.659976  DOI: Not available
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