Mechanical induction in limb morphogenesis: the role of growth-generated strains and pressures

Morphogenesis is regulated by intrinsic factors within cells and by inductive signals transmitted through direct contact, diffusible molecules, and gap junctions. In addition, connected tissues growing at different rates necessarily generate complicated distributions of physical deformations (strains) and pressures. In this Perspective we present the hypothesis that growth-generated strains and pressures in developing tissues regulate morphogenesis throughout development. We propose that these local mechanical cues influence morphogenesis by: (1) modulating growth rates; (2) modulating tissue differentiation; (3) influencing the direction of growth; and (4) deforming tissues. It is in this context that we review concepts and experiments of cell signaling and gene expression in various mechanical environments. Tissue and organ culture experiments are interpreted in light of the developmental events associated with the growth of the limb buds and provide initial support for the presence and morphological importance of growth-generated strains and pressures. The concepts presented are used to suggest future lines of research that may give rise to a more integrated mechanobiological view of early embryonic musculoskeletal morphogenesis.