Global analysis of cell behavior and protein dynamics reveals region-specific roles for Shroom3 and N-cadherin during neural tube closure.
Global analysis of cell behavior and protein dynamics reveals region-specific roles for Shroom3 and N-cadherin during neural tube closure.
复制标题
DOI：
10.7554/elife.66704
复制
发表时间：
2022-03-04
期刊：
影响因子：
7.7
通讯作者：
Wallingford, John B.
中科院分区：
文献类型：
--
作者：
Baldwin, Austin T.;Kim, Juliana H.;Seo, Hyemin;Wallingford, John B.
神经管闭合不全是一种常见且严重的出生缺陷，但我们对神经管闭合过程中遗传学和细胞生物学的相互作用了解甚少。此外，导致神经管缺陷（NTD）的突变往往会影响神经管的前部或后部区域，但很少同时影响两者，这表明NTD遗传学具有区域特异性。为了更好地了解神经管闭合过程中细胞行为的区域特异性，我们通过高分辨率组织水平延时显微镜分析了非洲爪蟾神经管闭合过程中肌动蛋白和N-钙粘蛋白的动态定位。为了研究基因功能的区域性，我们在shroom 3中产生了嵌合突变，shroom 3是神经管闭合的关键调节因子。这种新的分析方法阐明了颅/前和脊髓/后神经管闭合过程中细胞行为之间的几个差异，提供了对shroom 3功能的机械见解，并证明了组织水平成像和分析产生神经管闭合细胞生物学机制见解的能力。
Failures of neural tube closure are common and serious birth defects, yet we have a poor understanding of the interaction of genetics and cell biology during neural tube closure. Additionally, mutations that cause neural tube defects (NTDs) tend to affect anterior or posterior regions of the neural tube but rarely both, indicating a regional specificity to NTD genetics. To better understand the regional specificity of cell behaviors during neural tube closure, we analyzed the dynamic localization of actin and N-cadherin via high-resolution tissue-level time-lapse microscopy during Xenopus neural tube closure. To investigate the regionality of gene function, we generated mosaic mutations in shroom3, a key regulator or neural tube closure. This new analytical approach elucidates several differences between cell behaviors during cranial/anterior and spinal/posterior neural tube closure, provides mechanistic insight into the function of shroom3, and demonstrates the ability of tissue-level imaging and analysis to generate cell biological mechanistic insights into neural tube closure.