Publication highlights

Researchers have found that the small intestine grows in response to pregnancy in mice. This partially irreversible change may help mice support a pregnancy and prepare for a second. They found that pregnant mice had a longer small intestine from just seven days into the pregnancy. By the end of the pregnancy, around day 18, the small intestine was 18% longer, and it remained longer up to 35 days after lactation. The villi and crypts inside the small intestine also became longer and deeper at the same time, but returned to pre-pregnancy values just seven days after weaning. The researchers identified an increase in a membrane protein called SGLT3a early in pregnancy. This sodium and proton sensor was responsible for about 45% of the villi growth triggered by reproduction but wasn't necessary for entire small intestine lengthening. The team believe hormones may play a role in switching on the gene for SGLT3a.

Once upon a time, you were one cell, and of course when you were one cell, you were only one kind of cell. You are now made up of perhaps 400 kinds of cells. How did each cell decide what to be?

These questions have been studied for a long time. Waddington’s famous work of the 1950s suggested cells roll downhill to a Y-junction, where they choose between two potential fates. A research team at the Crick's contribution is to observe that often there is no Y-junction. They observe cases where one cell type, the majority, continues its development along a straight path while the other potential fate branches off from this. This new insight has been enabled by single-cell RNA-seq technology, which enables them to study gene expression at high resolution, a new mathematical insight, and software (TrajectoryGeometry) that they have created to exploit this insight.

Innervation of the gut is necessary for the regulation of digestive functions and for protection from micro-organisms which cause disease. To perform these important tasks, the gut is colonised during embryonic development by a small population of unspecified cells that expands rapidly and generates a vast number of specialised nerve cells, that control the movement of food through the gut. This population also generates support cells called glial cells. These protect the nerves and at the same time help the rest of gut tissue to fight infections and repair potential damage caused by them.

By characterising the molecular properties of these cell populations at several developmental stages and in adult animals, researchers at the Crick uncovered rules which control the assembly of the nervous system of the gut and how its constituent cell types acquire their properties. The team also showed that the support cells of the gut nervous system preserve the ability to form new nerves throughout life. These new findings will help us understand the development of some of the most severe gastrointestinal disorders and develop novel strategies for their treatment.

Researchers from the Pachnis lab have uncovered a fundamental role of glial cells in the gut nervous system in maintaining a healthy intestine. These cells have been found to coordinate the immune responses of the gut following pathogen invasion and could be key targets when exploring new treatments for inflammatory bowel conditions.