Mechanosensitive feedback organizes cell shape and motion during hindbrain neuropore morphogenesis

Area of Science:

• Developmental Biology
• Biophysics
• Cell Biology

Background:

• Neural tube closure is essential for vertebrate development, with defects leading to congenital malformations.
• The mechanisms organizing cell shape and motion for large-scale tissue remodeling during hindbrain neuropore (HNP) closure are not fully understood.
• Existing models implicate actomyosin contractility and cell crawling, but their sufficiency for observed cellular patterns is debated.

Purpose of the Study:

• To investigate the physical principles governing cell behavior and tissue dynamics during embryonic hindbrain neuropore closure.
• To determine if known force-generating mechanisms adequately explain observed cell elongation and nematic alignment at the HNP border.
• To establish a biophysical framework linking cellular organization to tissue-level morphodynamics.

Main Methods:

• Live and fixed imaging of mouse embryos.
• Cell-based biophysical modeling.
• Experimental validation of model predictions, including cytoskeletal organization and cell speed.

Main Results:

• Actomyosin contractility and cell crawling alone are insufficient to explain cell elongation and nematic alignment at the HNP border.
• Local anisotropic stress and cytoskeletal organization are required to generate observed cellular patterns and promote midline cell motion.
• A biophysical model successfully captured cell shape dynamics and emergent nematic order, confirmed by experimental data showing actin fiber alignment and increased midline cell speed.

Conclusions:

• Local anisotropic stress and cytoskeletal organization play critical roles in driving hindbrain neuropore closure.
• These findings reveal a physical framework connecting force generation, cell shape, and tissue morphodynamics during epithelial gap closure.
• A conserved link exists between tension generation and cellular patterning during embryonic development, as supported by comparative analysis with chick embryos.