Temporal dynamics of BMP/Nodal ratio drive tissue-specific gastrulation morphogenesis.

Anteroposterior (AP) elongation of the vertebrate body plan is driven by convergence and extension (C&E) gastrulation movements in both the mesoderm and neuroectoderm, but how or whether molecular regulation of C&E differs between tissues remains an open question. Using a zebrafish explant model of AP axis extension, we show that C&E of the neuroectoderm and mesoderm can be uncoupled ex vivo, and that morphogenesis of individual tissues results from distinct morphogen signaling dynamics. Using precise temporal manipulation of BMP and Nodal signaling, we identify a critical developmental window during which high or low BMP/Nodal ratios induce neuroectoderm- or mesoderm-driven C&E, respectively. Increased BMP activity similarly enhances C&E specifically in the ectoderm of intact zebrafish gastrulae, highlighting the in vivo relevance of our findings. Together, these results demonstrate that temporal dynamics of BMP and Nodal morphogen signaling activate distinct morphogenetic programs governing C&E gastrulation movements within individual tissues.

Vangl2 deficient zebrafish exhibit hallmarks of neural tube closure defects.

Neural tube defects (NTDs) are among the most devastating and common congenital anomalies worldwide, and the ability to model these conditions in vivo is 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 lacking vangl2, 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.