Dr David Edgar

 University Crest

Department of Human Anatomy and Cell Biology
Sherrington Buildings
Ashton Street
Liverpool
L69 3GE
UK

Telephone:
Fax:
E-mail:

 +44 (0)151 794 5508
+44 (0)151 794 5517
dhedgar@liv.ac.uk

Contents

Regulation of tissue development during early embryogenesis

Although the mechanisms regulating the differentiation of cells necessary for development of the zygote into a mature organism remain largely unknown, during recent years it has become increasingly clear that cell-cell and cell-extracellular matrix interactions play a pivotal role.

During the development of the preimplantation mammalian embryo, the first event which determines the direction of development of previously undifferentiated blastula cells is compaction. In this process the blastomeres begin to adhere strongly to each other to form a morula, and it is the outer cells of this compacted body which gives rise to the first differentiated tissue, the trophectoderm. The initial function of the trophectoderm is to pump ions and water into the morula in order to form the fully expanded blastocyst, necessary for hatching and successful uterine implantation. Pumping is only possible because the trophectodermal cells become polarised to constitute an epithelial layer, but the mechanisms of polarisation are unknown. To determine these mechanisms, we are investigating the factors necessary for cell polarisation in mouse embryonic stem cells and preimplantation embryos obtained from superovulated mice. As expected, the trophectoderm cells can be shown by immunohistochemistry to be sitting on a basement membrane, a thin sheet of extracellular matrix material. It is, however, unclear if this basement membrane is a cause or a consequence of trophectodermal cell polarisation.

Our previous work to create transgenic mouse knockout mutants offers a unique possibility to establish the casual events in trophectodermal development. We have shown that ablation of the gene coding for a subunit of the ubiquitous basement membrane protein laminin effectively blocks basement membrane formation in embryoid bodies derived from the cultured mouse embryonic stem cells. This work will now be extended to examine trophectodermal development of cultured preimplantation embryos by means of a combination of cell- and molecular-biological techniques established in the laboratory.

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This page was last updated by Lynne Jones