ABSTRACT
In regeneration, primordia cells have to be generated, and they progress to tissues and organs. In regenerative engineering, one has to be concerned with where the primordia cells come from and how to guide them to form tissues/organs of the right shape and size. This is a multi-dimensional issue that involves tissue interactions, cell fate specification, morphogenesis, tissue pattern organization, size regulation, and organ shaping. In this perspective, we focus on how organ shapes, simple or complex, can be explained by the topological deployment of localized signaling centers (LSCs). Cell behavior has been described in terms of cell proliferation, cell differentiation, cell apoptosis, cell adhesion, and cell migration. In regeneration, we deal with cell populations, but localized signaling centers can also be ascribed to specify localized proliferative zones, localized differentiation zones, localized apoptotic zones, localized cellular elongation zones, and localized epithelial–mesenchymal transition (EMT) zones. Their relative position, size, and duration of activity can vary. A combination of these LSCs then works coordinately to sculpt and build an organ shape. Analysis of four integument organs (beak, feather, mammary gland, and tooth) reveals different aspects of this concept. From these, we hope to learn how nature builds its architecture, and how to apply these principles toward guiding stem cells toward the bigger goal of regenerative engineering.
