Williams, M. K. | bioRxiv Science

bioRxiv2024

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. SUMMARY STATEMENTUsing zebrafish embryo and explant models, we demonstrate that temporal dynamics of morphogen signaling ratios distinguish between tissue-specific morphogenetic programs during vertebrate body plan formation.

developmental biology↗

bioRxiv2023

Vangl2 deficient zebrafish exhibit hallmarks of neural tube closure defects

Shaping of the future brain and spinal cord during neurulation is an essential component of early vertebrate development. In amniote embryos, primary neurulation occurs through a "fold-and-fuse" mechanism by which the edges of the neural plate fuse into the hollow neural tube. Failure of neural fold fusion results in neural tube defects (NTDs), which are among the most devastating and common congenital anomalies worldwide. Unlike amniotes, the zebrafish neural tube develops largely via formation of a solid neural keel that later cavitates to form a midline lumen. Although many aspects of primary neurulation are conserved in zebrafish, including neural fold zippering, it was not clear how well these events resemble analogous processes in amniote embryos. Here, we demonstrate that despite outward differences, zebrafish anterior neurulation closely resembles that of mammals. For the first time in zebrafish embryos, we directly observe enclosure of a lumen by the bilateral neural folds, which fuse by zippering between at least two distinct closure sites. Both the apical constriction that elevates the neural folds and the zippering that fuses them coincide with apical Myosin enrichment. We further show that embryos lacking vangl2, a core planar cell polarity and NTD risk gene, exhibit delayed and abnormal neural fold fusion that fails to enclose a lumen. These defects can also be observed in fixed embryos, enabling their detection without live imaging. Together, our data provide direct evidence for fold-and-fuse neurulation in zebrafish and its disruption upon loss of an NTD risk gene, highlighting the deep conservation of primary neurulation across vertebrates. HighlightsO_LIThe anterior neural tube of zebrafish undergoes "fold-and-fuse" neurulation to enclose a lumen, highlighting conservation of primary neurulation mechanisms across vertebrates. C_LIO_LIAnterior neural tube closure is delayed and abnormal in zebrafish embryos lacking the planar cell polarity gene vangl2, occurring by excessive "buttoning" rather than smooth "zippering" and failing to enclose a lumen. C_LIO_LINeural tube defects (NTDs) are visible in fixed vangl2 deficient embryos, enabling simple assessment of neural tube phenotypes with potential utility in screening NTD risk genes. C_LI

developmental biology↗