Community Research and Development Information Service - CORDIS

The surprisingly intricate human gut

The adult human gut has a staggering surface area of 220 square metres. Exploration of its biochemistry and cell development promises to increase knowledge on the exceptional role of the gut in tumour development.
The surprisingly intricate human gut
The inner lining of the human gut not only digests and absorbs nutrients, it comes into contact with the external environment in the form of pathogens, for example. The GUTENCODE (Decoding the transcriptional networks controlling the adult Drosophila midgut compartmentalization) project has investigated the fruit fly gut for the biochemistry involved in possible tumour development.

Like mammals, the Drosophila gut is renewed by stem cells and is divided into longitudinal compartments. Project researchers generated a detailed atlas of the Drosophila midgut. The morphometric, histological and genetic investigation showed that there are six regions that can be further sub-divided into 14 smaller compartments. A search into the reasons for differential properties of stem cells moving along the gut revealed an interesting new gene, Sox21a.

Further investigation revealed that Sox21a is responsible for controlling the differentiation of multipotent intestinal stem cells (ISCs) that develop into either an absorptive or a secretory cell via an intermediate phase called the enteroblast. The researchers found that loss of Sox21a blocks stem cells at the enteroblast state leading to the formation of tumours.

In the absence of Sox21a, progenitor cells cannot differentiate and then stimulate the formation of surrounding stem cells and this gives rise to hyperplastic growth. Sox21a-mutant-derived tumours are particularly aggressive in the anterior midgut but this is not evident in the posterior area. Using genetic tools, the scientists showed that this stalling of differentiation causes the release of chemicals. This in turn induces both proliferation of stem cells and tumour formation through the release of reactive oxygen species.

GUTENCODE researchers have therefore developed a model where blockage of cell differentiation causes aggressive tumour formation with different outcomes depending on the section of the gut. They expect that these results will be relevant to certain intestinal diseases in humans.

Related information


Gut, tumour development, stem cells, Sox21a, reactive oxygen species
Follow us on: RSS Facebook Twitter YouTube Managed by the EU Publications Office Top