Goblet cell carcinoids of the appendix: Tumor biology, mutations and management strategies

Figure 1 Schematic diagram of crypt-villus axis. The initial signaling mechanisms in a crypt-villus axis begin with Wnt and Notch pathways. The Wnt pathways maintain the gut stem cell compartment. The Paneth cell which constitutes part of the stem cell niche generates Wnt signals that act over a short range and keep cells in the crypt in a proliferative state. There exists a gradient in Wnt, Notch and noggin signaling which is highest in the crypt base and diminishes towards the crypt-villus junction. BMP signaling is low in the crypt and higher in the crypt villus junction. A definitive gradient exists for Eph-ephrin pathways too. The cells acquiring a differentiated fate switch off the expression of Eph-B and switch on the expression of Ephrin B ligands which progressively increases as they migrate up the axis.