Patterns of mitochondrial ATP predict tissue folding
- Bezia Lemma
- Megan Rothstein
- Pengfei Zhang
- Bridget Waas
- Marcus Kilwein
- Safiya Topiwala
- Sherry X. Zhang
- Anvitha Sudhakar
- Katharine Goodwin
- Elizabeth R. Gavis
- Ricardo Mallarino
- Andrej Košmrlj
- Celeste M. Nelson
2026-04-22
The construction of tissue shapes during embryonic development results from patterns of gene expression and mechanical forces fueled by chemical energy from ATP hydrolysis. We find that chemical energy is similarly patterned during apical constriction, which is widely used across the animal kingdom to fold epithelial tissues. Time-lapse imaging, spatial transcriptomics, and measurements of oxygen consumption rate reveal that mitochondrial density, potential, and ATP increase at the apical side of epithelial cells before actomyosin contraction and tissue folding, which is prevented by inhibiting oxidative phosphorylation. Mitochondrial enrichment and apical bias are conserved during apical constriction in flies, chicks, and mice, and these patterns can be used to predict computationally patterns of tissue folding. These findings highlight a spatial dimension of bioenergetics in development.