Neurulation is a highly synchronized biomechanical process leading to the formation of the brain and spinal cord, and its failure leads to neural tube defects (NTDs). Although we are rapidly learning the genetic mechanisms underlying NTDs, the biomechanical aspects are largely unknown. To understand the correlation between NTDs and tissue stiffness during neural tube closure (NTC), we imaged an NTD murine model using optical coherence tomography (OCT), Brillouin microscopy and confocal fluorescence microscopy. Here, we associate structural information from OCT with local stiffness from the Brillouin signal of embryos undergoing neurulation. The stiffness of neuroepithelial tissues in Mthfd1l null embryos was significantly lower than that of wild-type embryos. Additionally, exogenous formate supplementation improved tissue stiffness and gross embryonic morphology in nullizygous and heterozygous embryos. Our results demonstrate the significance of proper tissue stiffness in normal NTC and pave the way for future studies on the mechanobiology of normal and abnormal embryonic development.

Keywords:
Brillouin microscopy, Neural tube closure, Neural tube defects, Biomechanics, Mouse

Author contributions

Conceptualization: Y.S.A., C.D.C.; Methodology: Y.S.A., C.D.C., B.J.W., M.S., A.W.S., J.W.S., S.R.A.; Software: Y.S.A., M.S.; Validation: Y.S.A., C.D.C., B.J.W.; Formal analysis: Y.S.A., C.D.C., M.S., A.W.S., J.W.S., S.R.A.; Investigation: Y.S.A., C.D.C., B.J.W.; Resources: C.D.C., B.J.W.; Data curation: Y.S.A., C.D.C.; Writing - original draft: Y.S.A.; Writing - review & editing: Y.S.A., C.D.C., M.S., J.W.S., J.Z., S.R.A., G.S., R.H.F., K.V.L.; Visualization: Y.S.A., C.D.C., B.J.W., M.S., A.W.S., J.W.S., J.Z., S.R.A.; Supervision: S.R.A., G.S., R.H.F., K.V.L.; Project administration: G.S., R.H.F., K.V.L.; Funding acquisition: G.S., R.H.F., K.V.L.

Funding

This project was supported by the National Institutes of Health (R01 HD095520 to K.V.L., G.S. and R.H.F.). Deposited in PMC for release after 12 months.

Data availability

All relevant data can be found within the article and its supplementary information.

© 2024. Published by The Company of Biologists Ltd
2024
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