The Notochord Breaks Bilateral Symmetry by Controlling Cell Shapes in the Zebrafish Laterality Organ

• Lumen growth is required for Kupffer’s vesicle (KV) cells to acquire their shape
• Global embryo patterning cues do not set KV asymmetry
• The notochord locally induces cell shape changes in adjacent KV-forming cells
• The notochord polarizes ECM deposition adjacent to KV cells

SummaryKupffer’s vesicle (KV) is the zebrafish organ of laterality, patterning the embryo along its left-right (LR) axis. Regional differences in cell shape within the lumen-lining KV epithelium are essential for its LR patterning function. However, the processes by which KV cells acquire their characteristic shapes are largely unknown. Here, we show that the notochord induces regional differences in cell shape within KV by triggering extracellular matrix (ECM) accumulation adjacent to anterior-dorsal (AD) regions of KV. This localized ECM deposition restricts apical expansion of lumen-lining epithelial cells in AD regions of KV during lumen growth. Our study provides mechanistic insight into the processes by which KV translates global embryonic patterning into regional cell shape differences required for its LR symmetry-breaking function.

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