Semin Cell Dev Biol 2019 03 25;87:105-115. Epub 2018 Jul 25.
Department of Biological Sciences, Western Michigan University, 1903 W. Michigan Avenue, Kalamazoo, MI, 49008, USA. Electronic address:
A key requirement of tissue/organ regeneration is the ability to induce appropriate shape in situ. Regenerated structures need to be integrated with pre-existing ones, through the combined regulation of new tissue growth and the scaling of surrounding tissues. This requires a tightly coordinated control of individual cell functions such as proliferation and stem cell differentiation. While great strides have been made in elucidating cell growth and differentiation mechanisms, how overall shape is generated during regeneration remains unknown. This is because a significant gap remains in our understanding of how cell behaviors are coordinated at the level of tissues and organs. The highly regenerative planarian flatworm has emerged as an important model for defining and understanding regenerative shape mechanisms. This review provides an overview of the main processes known to regulate tissue and animal shape during planarian regeneration: adult stem cell regulation, the reestablishment of body axes, tissue remodeling in pre-existing structures, organ scaling and the maintenance of body proportion, and the bioelectrical regulation of animal morphology. In order for the field to move forward, it will be necessary to identify shape mutants as a means to uncover the molecular mechanisms that synchronize all these separate processes to produce the worm's final regenerative shape. This knowledge will also aid efforts to define the mechanisms that control the termination of regenerative processes.