Chromatin remodeling integrates vertebrate body axis elongation and cell fate determination

Abstract

The effective elongation of the vertebrate body axis depends on the precise coordination of cell movements and cell fate determination within the posterior tailbud region. However, the specific biological determinant that integrates these cellular processes during vertebrate tail bud elongation has remained unclear. Here, we demonstrate that the spatiotemporal heterogeneity of chromatin condensation states governs both cell fate and cell motility within the mesodermal progenitor zone (MPZ) and the presomitic mesoderm (PSM) during zebrafish tail bud elongation. By integrating biological experiments with computational modeling, we reveal that nuclear volume heterogeneity, mediated by chromatin remodeling, acts as an active driver of collective cell migration. Reducing chromatin condensation heterogeneity in the MPZ through modulation of chromatin modifications impairs collective cell movements and delays tailbud elongation. Single cell ATAC-seq and RNA-seq analyses reveal that global chromatin accessibility heterogeneity and region-specific chromatin remodeling differences in the PSM and MPZ are functionally associated with gene expression pathways involving in cell lineage specification. These findings establish a molecular connection between cell fate determination and tissue-scale cellular dynamics. Collectively, our findings unveil a unifying framework for understanding the coordination of cell fate determination and large-scale cellular movements during tissue morphogenesis.