Vangl2 deficient zebrafish exhibit hallmarks of neural tube closure defects

Abstract

AbstractNeural tube defects (NTDs) are among the most devastating and common congenital anomalies worldwide, and the ability to model these conditionsin vivois essential for identifying causative genetic and environmental factors. Although zebrafish are ideal for rapid candidate testing, their neural tubes develop primarily via a solid neural keel rather that the fold-and-fuse method employed by mammals, raising questions about their suitability as an NTD model. Here, we demonstrate that despite outward differences, zebrafish anterior neurulation closely resembles that of mammals. For the first time, we directly observe fusion of the bilateral neural folds to enclose a lumen in zebrafish embryos. The neural folds fuse by zippering between multiple distinct but contiguous closure sites. Embryos lackingvangl2, a core planar cell polarity and NTD risk gene, exhibit delayed neural fold fusion and abnormal neural groove formation, yielding distinct openings and midline bifurcations in the developing neural tube. These data provide direct evidence for fold-and-fuse neurulation in zebrafish and its disruption upon loss of an NTD risk gene, highlighting conservation of vertebrate neurulation and the utility of zebrafish for modeling NTDs.Summary statementThe anterior neural tube of zebrafish exhibits fold-and-fuse neurulation which is disrupted upon loss of Vangl2, highlighting conservation of vertebrate neurulation and the potential to model neural tube defects in zebrafish.