Collagen organization regulates morphogenesis and cell fate in mesenchymal cell collectives in vivo

Jacqueline Tabler (Max Planck Institute of Molecular Cell Biology and Genetics, Dresden)

23 May 2024


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12:00 - 13:00
Conference room Rosalind Franklin
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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 such as the organization of collagen. Indeed, collagen organization is sufficient not only to regulate spatiotemporal patterns of differentiation in the skull but also the emergence and maintenance of the skull’s stem cell niches, the sutures.  We find that collagen cross-linking rather than stiffness defines the differentiation state of these niches where collagen by promoting Lamin A polymerization at the nuclear envelope. Unlike MSCs in vitro where enriched Lamin A polymerization drives osteoblast differentiation, we find that Lamin A enrichment maintains stemless indicating that mechanical control of differentiation in mesenchymal cells is context-dependent and cannot be understood through in vitro assays alone.

Jacqueline Tabler is invited by Antoine Zalc.