Hnf4α is a key gene that can generate columnar metaplasia in oesophageal epithelium.

Barrett's metaplasia is the only known morphological precursor to oesophageal adenocarcinoma and is characterized by replacement of stratified squamous epithelium by columnar epithelium. The cell of origin is uncertain and the molecular mechanisms responsible for the change in cellular phenotype are poorly understood. We therefore explored the role of two transcription factors, Cdx2 and HNF4α in the conversion using primary organ cultures.

Barrett's metaplasia: molecular mechanisms and nutritional influences.

Barrett's metaplasia is discussed in the context of a general theory for the formation of metaplasias based on developmental biology. The phenotype of a particular tissue type becomes established during embryonic development by the expression of a specific set of transcription factors. If this combination becomes altered, then the tissue type can be altered.

Isolation, culture, and characterisation of mouse embryonic oesophagus and intestine.

The gastrointestinal tract of vertebrates is lined by epithelium that develops from the endodermal germ layer. The oesophagus and intestine form part of the gastrointestinal tract and studying the normal development of both tissues is difficult due to lack of suitable in vitro model systems. One of the criteria for a reliable culture model includes the ability to carry out real-time observations in vitro.

Epithelial metaplasia and the development of cancer.

Metaplasia means the conversion, in postnatal life, of one cell type to another. Understanding the steps leading to metaplasia is important for two reasons. Firstly, it tells us something about the normal developmental biology of the tissues that interconvert.

In vitro culture of embryonic mouse intestinal epithelium: cell differentiation and introduction of reporter genes.

Background: Study of the normal development of the intestinal epithelium has been hampered by a lack of suitable model systems, in particular ones that enable the introduction of exogenous genes. Production of such a system would advance our understanding of normal epithelial development and help to shed light on the pathogenesis of intestinal neoplasia. The criteria for a reliable culture system include the ability to perform real time observations and manipulations in vitro, the preparation of wholemounts for immunostaining and the potential for introducing genes.

The molecular basis of transdifferentiation.

There is now excellent experimental evidence demonstrating the remarkable ability of some differentiated cells to convert to a completely different phenotype. The conversion of one cellular phenotype to another is referred to as 'transdifferentiation' and belongs to a wider class of cell-type switches termed 'metaplasias'. Defining the molecular steps in transdifferentiation will help us to understand the developmental biology of the cells that interconvert, as well as help identify key regulatory transcription factors that may be important for the reprogramming of stem cells.