Limited Column Formation in Embryonic Growth Plates Suggests Divergent Bone Growth Mechanisms

Summary: A groundbreaking study published in eLife challenges our understanding of bone growth mechanisms during embryonic development. Key findings include:

1. Contrary to previous beliefs, chondrocytes in embryonic growth plates rarely form the typical columnar structures associated with bone elongation.
2. 3D imaging and advanced analysis revealed that most embryonic chondrocytes form clusters oriented perpendicular to the growth direction, rather than columns.
3. Incomplete rotation of cell division planes in embryonic chondrocytes leads to this non-columnar arrangement.
4. Postnatal growth plates show a mix of complex columns and small, disorganized clusters.
5. The study suggests that modulation of division plane rotation determines whether clusters or columns form, potentially regulating bone expansion and elongation differently during pre- and postnatal development.

This research provides new insights into the cellular mechanisms underlying growth plate activity and bone development, potentially impacting our understanding of skeletal disorders and therapeutic approaches.

Abstract: Chondrocyte columns, which are a hallmark of growth plate architecture, play a central role in bone elongation. Columns are formed by clonal expansion following rotation of the division plane, resulting in a stack of cells oriented parallel to the growth direction. In this work, we analyzed hundreds of Confetti multicolor clones in growth plates of mouse embryos using a pipeline comprising 3D imaging and algorithms for morphometric analysis. Surprisingly, analysis of the elevation angles between neighboring pairs of cells revealed that most cells did not display the typical stacking pattern associated with column formation, implying incomplete rotation of the division plane. Morphological analysis revealed that although embryonic clones were elongated, they formed clusters oriented perpendicular to the growth direction. Analysis of growth plates of postnatal mice revealed both complex columns, composed of ordered and disordered cell stacks, and small, disorganized clusters located in the outer edges. Finally, correlation between the temporal dynamics of the ratios between clusters and columns and between bone elongation and expansion suggests that clusters may promote expansion, whereas columns support elongation. Overall, our findings support the idea that modulations of division plane rotation of proliferating chondrocytes determines the formation of either clusters or columns, a multifunctional design that regulates morphogenesis throughout pre- and postnatal bone growth. Broadly, this work provides a new understanding of the cellular mechanisms underlying growth plate activity and bone elongation during development.

Reference: Rubin, S., Agrawal, A., Seewald, A., Lian, M.-J., Gottdenker, O., Villoutreix, P., Baule, A., Stern, T., & Zelzer, E. (2024). Limited column formation in the embryonic growth plate implies divergent growth mechanisms during pre- and postnatal bone development. eLife, 13:e95289. https://doi.org/10.7554/eLife.95289

#BoneDevelopment #Chondrocytes #GrowthPlate #CellBiology #DevelopmentalBiology #3DImaging #BoneElongation #TissueMorphogenesis #EmbryonicDevelopment #SkeletalResearch