关键词: Biomechanics Brillouin microscopy Mouse Neural tube closure Neural tube defects

Mesh : Animals Female Mice Biomechanical Phenomena Embryo, Mammalian / metabolism Formate-Tetrahydrofolate Ligase / genetics metabolism Formates / metabolism Methylenetetrahydrofolate Dehydrogenase (NADP) / genetics metabolism Mice, Knockout Microscopy, Confocal Mutation / genetics Neural Tube / metabolism Neural Tube Defects / genetics metabolism pathology Neurulation / genetics Tomography, Optical Coherence / methods

来  源:   DOI:10.1242/dev.202475   PDF(Pubmed)

Abstract:
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.
摘要:
神经是一个高度同步的生物力学过程,导致大脑和脊髓的形成,其失败导致神经管缺陷(NTDs)。尽管我们正在迅速了解NTDs的遗传机制,生物力学方面在很大程度上是未知的。为了了解神经管闭合(NTC)过程中NTDs与组织硬度之间的相关性,我们使用光学相干断层扫描(OCT)成像NTD小鼠模型,布里渊显微镜,和共聚焦荧光显微镜。这里,我们将OCT的结构信息与接受神经发育的胚胎布里渊信号的局部硬度相关联.Mthfd1l空胚胎的神经上皮组织硬度明显低于野生型胚胎。此外,外源性甲酸盐补充改善了无效和杂合胚胎的组织硬度和大体胚胎形态。我们的结果证明了正常NTC中适当组织硬度的重要性,并为将来研究正常和异常胚胎发育的机械生物学铺平了道路。
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