Postembryonic organogenesis of the digestive tube: why does it occur in worms and sea cucumbers but fail in humans?

We provide an integrative view of mechanisms that enable regeneration of the digestive tube in various animal models, including vertebrates, tunicates, echinoderms, insects, and flatworms. Two main strategies of regeneration of the endodermal luminal (mucosal) epithelium have evolved in metazoans. One of them involves proliferation of resident epithelial cells, while the other relies on recruitment of cells from extramucosal sources. In any of these two scenarios, either pluri-/multipotent stem cells or specialized differentiated cells can be used as the starting material. Posttraumatic visceral regeneration shares some common mechanisms with normal embryonic development as well as with organ homeostatic maintenance, but there are signaling pathways and/or cellular pools that are specific to the regenerative phenomena. Comparative analysis of the literature suggests that mammals share with spontaneously regenerating animals many of the regeneration-related adaptations and are able to efficiently repair components of their digestive tube at the level of individual tissues, but fail to do so at the whole-organ scale. We review what might cause this failure in the context of the current state of knowledge about various regenerative models.