AI Insight
This study identifies a sequence of six cell behaviors that drive spinal cord fusion during mouse embryonic development through a process called "zippering." Researchers found that the protein CFL1, which severs F-actin filaments in cells, is essential for proper zippering speed and completion. When CFL1 is deleted from surface ectoderm cells, filopodia become overly stable, cells fail to constrict properly at fusion points, and approximately 30% of embryos develop spina bifida, with zippering speed reduced by about 30%.
Why it matters
Understanding the cellular mechanisms of spinal cord closure could provide insights into preventing neural tube defects like spina bifida, which affects approximately 1 in 1,000 pregnancies worldwide. This research identifies CFL1 as a potential target for understanding why spinal closure fails in some embryos and may inform future preventive strategies.
by Abigail R. Marshall, Andrea Krstevski, Henry Crosswell, Rahul Shah, Eirini Maniou, Nicholas D. E. Greene, Andrew J. Copp, Gabriel L. Galea
Epithelial fusion is critical for formation of many embryonic tissues. The developing mammalian spinal cord fuses by zippering, through cell behaviours dependent on F-actin turnover. We propose a caudal-to-rostral sequence of surface ectoderm cell behaviours which drive zippering progression in mice, and test the requirement for the F-actin severing protein CFL1 in this process. Key zipper-advancing behaviours are: (i) constriction of supracellular actomyosin cables; (ii) extension of filopodial/lamellipodial protrusions at periodic intervals; (iii) constriction of leading-edge cell borders bringing together protrusions which establish ‘pioneering’ contacts across the midline; (iv) cell-cell and v. cell-ECM adhesion remodelling; (vi) zipper advancement through cell partner exchange. In wild-type embryos, CFL1 is enriched at the leading edge of surface ectoderm cells adjacent to the zippering point and localised within some protrusions. Conditional Cfl1 deletion in the surface ectoderm produces denser F-actin stress fibres, makes filopodial protrusions excessively stable, diminishes their exploratory movements which may establish nascent contacts, and impairs junctional constriction of cells at the point of fusion. Zippering speed is reduced ~30% in conditional Cfl1-deleted embryos and ~30% develop spina bifida. We therefore propose that impaired filopodial dynamicity and junctional constriction limits the sequence of behaviours driving spinal zippering, predisposing to spina bifida.
Source: CFL1-dependency of discrete cell behaviours driving mouse spinal zippering