YAP mediated mechano-homeostasis - conditioning 3D animal body shape

Cells of terrestrial animals are constantly exposed to external forces including gravity. However, the complex 3D structure of the body and its organs form without being flattened. A century ago, the mathematical biologist D'Arcy Thompson predicted in 'On Growth and Form' that terrestrial animal body shapes are entirely conditioned by gravity [1], but the prediction remained to be proved due to the lack of an appropriate animal model. In this review, we outline a new mechanism of morphogenesis which ensures the generation of vertebrate 3D body shape that can withstand gravity and in which Hippo-YAP signaling acts as a mechano-effector controlling mechano-homeostasis. We will highlight the recent papers that advanced the field and discuss the impact of this previously unrecognized function of YAP-mediated signaling on the established concept of organogenesis, tissue homeostasis and disease.