PERSPECTIVE 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, con-nected 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 morpho-genesis 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 expres-sion in various mechanical environments. Tissue and organ culture experiments are interpreted in light of the develop-mental events associated with the growth of the limb buds and provide initial support for the presence and morpholog-ical 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 mechano-biological view of early embryonic musculoskeleta