Mechanometabolic control of vertebrate limb elongation

Animal tissues can be viewed as specialized materials that, like certain inert materials, possess the remarkable ability to quickly shift between fluid and solid states—a process known as phase transition. In their fluid state, tissues can be molded, much like glass in glassblowing, before solidifying to stabilize their structure. Phase transitions are now recognized as essential for shaping embryonic structures, although the molecular signals and cellular mechanisms driving them remain elusive. Emerging evidence suggest that metabolism may play a key role, beyond its traditional energy-providing function, in directing how tissues take shape. This proposal aims to unveil how metabolic activity orchestrates tissue sculpting through phase transitions, using the embryonic chicken limb as a model. {Aim 1} will explore how localized metabolic activity determines the physical properties of the tissue, modulating its malleability during embryonic limb development. {Aim 2} will investigate the cellular processes that enable the tissue to maintain/acquire specific physical properties. {Aim 3} will probe the interaction between metabolic activity and established genetic programs in shaping the limb. Achieving these aims and addressing how metabolism controls tissue fluidity will fill a gaping hole in our understanding of animal form, with far-reaching implications for basic biology and tissue engineering.