Cell Biology and Physiology Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Cell Biology and Physiology Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Development. 2019 Dec 11;146(23):dev176685. doi: 10.1242/dev.176685.
Understanding how events at the molecular and cellular scales contribute to tissue form and function is key to uncovering the mechanisms driving animal development, physiology and disease. Elucidating these mechanisms has been enhanced through the study of model organisms and the use of sophisticated genetic, biochemical and imaging tools. Here, we present an accessible method for non-invasive imaging of at high resolution using micro-computed tomography (µ-CT). We show how rapid processing of intact animals, at any developmental stage, provides precise quantitative assessment of tissue size and morphology, and permits analysis of inter-organ relationships. We then use µ-CT imaging to study growth defects in the brain through the characterization of () and (), orthologs of the two most commonly mutated genes in human microcephaly patients. Our work demonstrates the power of combining µ-CT with traditional genetic, cellular and developmental biology tools available in model organisms to address novel biological mechanisms that control animal development and disease.
了解分子和细胞尺度上的事件如何导致组织形态和功能，是揭示驱动动物发育、生理和疾病的机制的关键。通过对模式生物的研究和复杂的遗传、生化和成像工具的使用，这些机制已经得到了阐明。在这里，我们提出了一种使用微计算机断层扫描（µ-CT）进行高分辨率非侵入性成像的方法。我们展示了如何通过快速处理完整动物（处于任何发育阶段），精确地定量评估组织大小和形态，并允许分析器官之间的关系。然后，我们使用 µ-CT 成像来研究大脑中的生长缺陷，通过对（）和（）的特征化，这两种基因是人类小头畸形患者中最常突变的基因的同源物。我们的工作表明，将 µ-CT 与模型生物中可用的传统遗传、细胞和发育生物学工具相结合，以解决控制动物发育和疾病的新的生物学机制，具有强大的力量。
