CFL1-dependency of discrete cell behaviours driving mouse spinal zippering
- 1Developmental Biology and Cancer, UCL GOS Institute of Child Health, London, United Kingdom
- 2School of Biotechnology, Dublin City University, Dublin, Ireland
Abstract
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.
Spinal cord fusion requires coordinated cell behaviours, but the mechanisms driving zippering remain unclear. This study shows that CFL1-dependent actin remodelling promotes zippering progression in mouse and helps prevent spina bifida.
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BibTeX
@article{marshall2026cfl1dependency,
title = {{CFL1-dependency of discrete cell behaviours driving mouse spinal zippering}},
author = {Abigail R. Marshall and Andrea Krstevski and Henry Crosswell and Rahul Shah and Eirini Maniou and Nicholas D. E. Greene and Andrew J. Copp and Gabriel L. Galea},
journal = {PLOS Biology},
year = {2026},
month = nov,
doi = {10.1371/journal.pbio.3004092},
url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004092},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - CFL1-dependency of discrete cell behaviours driving mouse spinal zippering
AU - Abigail R. Marshall
AU - Andrea Krstevski
AU - Henry Crosswell
AU - Rahul Shah
AU - Eirini Maniou
AU - Nicholas D. E. Greene
AU - Andrew J. Copp
AU - Gabriel L. Galea
PY - 2026
DA - 2026/11/02
JO - PLOS Biology
DO - 10.1371/journal.pbio.3004092
UR - https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004092
AB - 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. Spinal cord fusion requires coordinated cell behaviours, but the mechanisms driving zippering remain unclear. This study shows that CFL1-dependent actin remodelling promotes zippering progression in mouse and helps prevent spina bifida.
SN - 1545-7885
ER -