The role of the EGFR signaling pathway in stem cell differentiation during planarian regeneration and homeostasis

Cell signaling is essential for cells to adequately respond to their environment. One of the most evolutionarily conserved signaling pathways is that of the epidermal growth factor receptor (EGFR). Transmembrane receptors with intracellular tyrosine kinase activity are activated by the binding of their corresponding ligands. This in turn activates a wide variety of intracellular cascades and induces the up or downregulation of target genes, leading to a specific cellular response. Freshwater planarians are an excellent model in which to study the role of cell signaling in the context of stem-cell based regeneration. Owing to the presence of a population of pluripotent stem cells called neoblasts, these animals can regenerate the entire organism from a tiny piece of the body. Here, we review the current state of knowledge of the planarian EGFR pathway. We describe the main components of the pathway and their functions in other animals, and focus in particular on receptors and ligands identified in the planarian Schmidtea mediterranea. Moreover, we summarize current data on the function of some of these components during planarian regeneration and homeostasis. We hypothesize that the EGFR pathway may act as a key regulator of the terminal differentiation of distinct populations of lineage-committed progenitors. (C) 2018 Elsevier Ltd. All rights reserved.