Fate, Phases, and Form in Vertebrate Organ Morphogenesis-Uncovering a Role of Morphogenesis at the Supracellular Scale

How morphology unfolds from fertilization to birth is one of the most fundamental questions in the life sciences. Self-organization in embryonic development, whereby organs robustly adopt forms through intrinsic processes, is a central feature that remains enigmatic. To achieve greater clarity of such processes, new conceptual and experimental approaches may be needed. Much of work in developmental biology in the past three to four decades has focused on cell and subcellular levels of organization. In line with work of some key conceptual thinkers, we revisit the notions of epigenetics. Rather than confining it to the molecular mechanisms of chromatin remodeling, we propose a broader understanding that includes processes beyond the cellular scale that possess their own generative power. Among the various scales at play, we propose to shift our focus to the mechanical and material processes at the supracellular scale. The hair or feather follicle in the skin represents one of the most apparent morphological features in development, and its spacing serves as a classic model system to study pattern formation. Mesenchymal-ECM relations are a key regulatory niche that remains poorly understood. By developing an ex vivo essay that reconstitutes the initiation of feather follicle pattern, we demonstrated that mesenchymal cell-ECM interplay can create supracellular structures independent of any morphogen activities. This challenges the classic chemical model where a morphogen pre-pattern dictates follicle patterning, prompting the question of what functional roles morphogens serve. found that morphogens enable the creation of membrane-less tissue compartments within the mesenchyme of the follicle with distinct biophysical properties, such as elasticity, viscosity and contractility. Specifically, fibroblast growth factor (FGF) promotes a stiff and solid hemispheric core compartment, whereas bone morphogenetic protein (BMP) promotes a surrounding fluid and active contractile margin compartment. Through their geometric ...