Developmental Biology research aims to understand the events and signaling cues taking place during the development of living organisms and organs. Historically, Developmental Biology relied heavily on complex model organisms like clawed frogs, fruit flies or mice. Today, researchers interested in the development of organs increasingly utilize organoids. These are artificial three-dimensional model systems that can imitate the cellular composition and tissue architecture of organs while also being easier to maintain and to manipulate experimentally.
Intestinal (gut) organoids have become indispensable tools for studying both normal gut development and the mechanisms that lead to morbidities (e.g., inflammatory bowel disease). Intestinal organoids are grown from single intestinal stem cells. With the proper signaling cues applied, they eventually form organoids consisting of a single layer of enterocytes (differentiated intestinal cells) surrounding a hollow lumen that resembles the lumen of a real gut (Figure 1A).
The Wnt pathway is a well-known signaling pathway regulating intestine development and maintenance. Functions and effects of Wnt are very intricate and context-dependent (for detailed reading, see reference below). Simply put, Wnt contributes to maintaining healthy tissue stem cells and the transition and differentiation of stem cells into mature enterocytes (intestinal tissue cells). On the other hand, excessive Wnt activity (e.g., by genetic mutations) contributes to intestinal cancer.
In this application story, we showcase a simple imaging experiment performed on intestinal organoids treated with and without a Wnt-inhibiting drug, with the experimental goal to study the role of Wnt signaling in organoid formation.