Self-propagating wave drives morphogenesis of skull bones in vivo

• Published in: Nature communications Vol. 16; no. 1; pp. 4330 - 11
• Main Authors: Dang, Yiteng, Lattner, Johanna, Lahola-Chomiak, Adrian A., Afonso, Diana Alves, Ulbricht, Elke, Taubenberger, Anna, Rulands, Steffen, Tabler, Jacqueline M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.05.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/51; 14; 14/19; 14/69; 631/136/1660; 631/136/818; 631/57/343/1361; 64; 64/60; Animals; Bones; Cell Differentiation; Cell fate; Cell migration; Cell Movement - physiology; Collagen - metabolism; Feedback; Humanities and Social Sciences; Material properties; Mechanical properties; Mice; Morphogenesis; Morphogenesis - physiology; multidisciplinary; Neuroimaging; Organogenesis; Osteoblasts - cytology; Osteoblasts - metabolism; Osteoblasts - physiology; Osteogenesis; Science; Science (multidisciplinary); Self propagation; Skull; Skull - cytology; Skull - embryology; Wave propagation
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-025-59164-9

Cellular motion is a key feature of tissue morphogenesis and is often driven by migration. However, migration need not explain cell motion in contexts where there is little free space or no obvious substrate, such as those found during organogenesis of mesenchymal organs including the embryonic skull. Through ex vivo imaging , biophysical modeling, and perturbation experiments, we find that mechanical feedback between cell fate and stiffness drives bone expansion and controls bone size in vivo. This mechanical feedback system is sufficient to propagate a wave of differentiation that establishes a collagen gradient which we find sufficient to describe patterns of osteoblast motion. Our work provides a mechanism for coordinated motion that may not rely upon cell migration but on emergent properties of the mesenchymal collective. Identification of such alternative mechanisms of mechanochemical coupling between differentiation and morphogenesis will help in understanding how directed cellular motility arises in complex environments with inhomogeneous material properties. How the bones of the skull vault expand to cover the brain is poorly understood. Here, the authors demonstrate that such bones grow through a mechanical feedback mechanism that propagates a wave of differentiation and emergent cell motion.