Mechanical Regulation of Limb Bud Formation

Early limb bud development has been of considerable interest for the study of embryological development and especially morphogenesis. The focus has long been on biochemical signalling and less on cell biomechanics and mechanobiology. However, their importance cannot be understated since tissue shape changes are ultimately controlled by active forces and bulk tissue rheological properties that in turn depend on cell-cell interactions as well as extracellular matrix composition. Moreover, the feedback between gene regulation and the biomechanical environment is still poorly understood. In recent years, novel experimental techniques and computational models have reinvigorated research on this biomechanical and mechanobiological side of embryological development. In this review, we consider three stages of early limb development, namely: outgrowth, elongation, and condensation. For each of these stages, we summarize basic biological regulation and examine the role of cellular and tissue mechanics in the morphogenetic process.