Oscillatory cortical forces promote three dimensional cell intercalations that shape the murine mandibular arch

Area of Science:

• Developmental Biology
• Biophysics
• Cell Biology

Background:

• Organ primordia form from confluent cells, but mechanisms shaping cellular volumes are unclear.
• Understanding 3D tissue morphogenesis is crucial for developmental biology.

Purpose of the Study:

• To investigate the mechanisms of 3D cell intercalation in shaping the mouse mandibular arch.
• To identify molecular cues and biophysical forces driving mesenchymal cell rearrangement.

Main Methods:

• Genetically encoded vinculin tension sensor knock-in in mice.
• Loss- and gain-of-function studies for Wnt5a.
• Analysis of cell polarity, cytoskeletal oscillations, and calcium transients.
• Investigated YAP/TAZ and PIEZO1 involvement.

Main Results:

• 3D mesenchymal cell intercalations are essential for mandibular arch shaping.
• Cortical force oscillations promote cell intercalation.
• Wnt5a coordinates cell polarity and cytoskeletal oscillation, reducing tissue rigidity.
• YAP/TAZ and PIEZO1 mediate Wnt5a effects on cell orientation and intercalation.

Conclusions:

• Developmental pathways regulate biophysical properties to shape organ primordia.
• Wnt5a, actomyosin dynamics, and mechanosensitive pathways are key regulators of 3D cell intercalation.
• This study provides insights into the forces driving embryonic organ development.