The intestinal tract undergoes many changes during development. To accommodate the growing body, it has to elongate and widen. This also serves to increase the surface area for nutrient absorption. The key process that facilitates intestinal tissue expansion is called crypt fission. Importantly, crypt fission is also involved in adenoma growth. Despite the importance of crypt fission, the mechanisms controlling it are poorly understood. Understanding how crypt fission is regulated in normal tissue can help us to determine how the process changes in cancer.
The Näthke lab discovered the cellular behaviour during crypt fission. They identified a specific cellular arrangement in the intestinal stem cell niche that is associated with crypt fission and reveals how it is controlled. There are two different cell types at the crypt base, Lgr5+ and Paneth cells, which play distinct roles in this process. They found that both the location and differences between these cells in proliferation, stiffness, and adhesion are important for fission. Based on their data, they propose a model in which stiffer and more adhesive Paneth cells are necessary to shape the crypt base and establish where fission occurs, whereas softer Lgr5+ cells allow shape changes and proliferation to expand newly formed crypts. Their model is an important step in understanding how crypt fission is initiated in normal tissue and provides a framework to understand how the process changes in tumorigenesis. The emerging principles may also apply to the branching morphogenesis that drives the growth of other organs like the mammary gland, lung, and kidney.
Full article can be viewed in PLOS Biology.