Measuring intraventricular pressure in developing mouse embryos: Uncovering a repetitive mechanical cue for brain...

In living organisms, including humans, the developmental processes that construct their morphology from a single fertilized egg are influenced not only by genetic regulation but also by various external factors. One such factor is mechanical stimulation. Although mechanical forces are suggested to contribute to brain formation during development, quantitative information on intraventricular pressure during neurogenesis remains limited. We developed a high time-resolution system efficiently using a piezoresistive sensor to measure brain intraventricular pressure in mouse embryos from E12.5 to E16.5 (embryonic stages in days). Ex utero measurements revealed intraventricular pressure increasing from 53.76 ± 4.16 Pa at E12.5 to 158.10 ± 19.94 Pa by E16.5. In utero analyses uncovered striking periodicity in sync with uterine contractions, reaching up to 1430 ± 195.2 Pa at E12.5, indicating dynamic mechanical stimuli beyond ex utero observations. Additionally, perforation experiments at E9.0-E15.5 showed rapid neuroepithelial thickening and apical surface contraction upon pressure release, indicative of a tensile effect by the positive intraventricular pressure. This effect diminished after E15.5, implying that tension wanes or the neuroepithelium becomes more robust. These results highlight the dynamic nature of embryonic intraventricular pressure, governed by internal fluid production and uterine forces, and emphasize the importance of mechanical cues in neuroepithelial architecture. Our findings provide a steppingstone to clarify how mechanical forces integrate with genetic and molecular processes to shape normal brain development and may render new perspectives on brain evolution.