Aberrant tissue stiffness impairs neural tube development in Mthfd1l mutant mouse embryos

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 compared to that of wild-type embryos, while exogenous formate supplementation improved tissue stiffness and gross embryonic morphology in both nullizygous and heterozygous embryos. Our results demonstrate the significance of proper tissue stiffness for normal NTC and pave the way for future studies on the mechanobiology of normal and abnormal embryonic development. ### Competing Interest Statement Drs. Finnell and Wlodarczyk participated in TeratOmic Consulting LLC, a now defunct consulting company. Additionally, Dr. Finnell serves on the editorial board for the journal Reproductive and Developmental Medicine and receives travel funds to attend editorial board meetings. Drs. Singh and Larin have a financial interest in ElastEye LLC., which is not related to this work. All other authors have no conflict of interest to declare.