Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 114, Issue 26, Pages E5177-E5186Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1700934114
Keywords
neural tube; biomechanics; F-actin; Zic2; mouse
Categories
Funding
- Wellcome Trust Postdoctoral Training Fellowship for Clinicians [107474/Z/15/Z]
- Wellcome Trust [087525]
- Medical Research Council [J003794]
- Bo Hjelt Spina Bifida Foundation
- Great Ormond Street Hospital Children's Charity
- MRC [G0801124] Funding Source: UKRI
- Wellcome Trust [107474/Z/15/Z] Funding Source: Wellcome Trust
- Medical Research Council [G0801124] Funding Source: researchfish
Ask authors/readers for more resources
Neural tube (NT) formation in the spinal region of the mammalian embryo involves a wave of zippering that passes down the elongating spinal axis, uniting the neural fold tips in the dorsal midline. Failure of this closure process leads to open spina bifida, a common cause of severe neurologic disability in humans. Here, we combined a tissue-level strain-mapping workflow with laser ablation of live-imaged mouse embryos to investigate the biomechanics of mammalian spinal closure. Ablation of the zippering point at the embryonic dorsal midline causes far-reaching, rapid separation of the elevating neural folds. Strain analysis revealed tissue expansion around the zippering point after ablation, but predominant tissue constriction in the caudal and ventral neural plate zone. This zone is biomechanically coupled to the zippering point by a supracellular F-actin network, which includes an actin cable running along the neural fold tips. Pharmacologic inhibition of F-actin or laser ablation of the cable causes neural fold separation. At the most advanced somite stages, when completion of spinal closure is imminent, the cable forms a continuous ring around the neuropore, and simultaneously, a new caudal-to-rostral zippering point arises. Laser ablation of this new closure initiation point causes neural fold separation, demonstrating its biomechanical activity. Failure of spinal closure in pre-spina bifida Zic2(Ku) mutant embryos is associated with altered tissue biomechanics, as indicated by greater neuropore widening after ablation. Thus, this study identifies biomechanical coupling of the entire region of active spinal neurulation in the mouse embryo as a prerequisite for successful NT closure.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available