Department of Medical Neurobiology, IMRIC and ELSC, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
Development. 2011 Oct;138(19):4155-66. doi: 10.1242/dev.065169. Epub 2011 Aug 18.
The plane of cell divisions is pivotal for differential fate acquisition. Dermomyotome development provides an excellent system with which to investigate the link between these processes. In the central sheet of the early dermomyotome, single epithelial cells divide with a planar orientation. Here, we report that in the avian embryo, in addition to self-renewing, a subset of progenitors translocates into the myotome where they generate differentiated myocytes. By contrast, in the late epithelium, individual progenitors divide perpendicularly to produce both mitotic myoblasts and dermis. To examine whether spindle orientations influence fate segregation, early planar divisions were randomized and/or shifted to a perpendicular orientation by interfering with LGN function or by overexpressing inscuteable. Clones derived from single transfected cells exhibited an enhanced proportion of mixed dermomyotome/myotome progeny at the expense of `like' daughter cells in either domain. Loss of LGN or Gαi1 function in the late epithelium randomized otherwise perpendicular mitoses and favored muscle development at the expense of dermis. Hence, LGN-dependent early planar divisions are required for the proper allocation of progenitors into either dermomyotome or myotome, whereas late perpendicular divisions are necessary for the normal balance between muscle and dermis production.
细胞分裂面对于获得不同命运至关重要。皮肌节的发育为研究这些过程之间的联系提供了一个极好的系统。在早期皮肌节的中央层,单个上皮细胞以平面取向分裂。在这里,我们报告说,在禽类胚胎中,除了自我更新外,一小部分祖细胞迁移到肌节中,在那里它们产生分化的肌细胞。相比之下,在晚期上皮中,单个祖细胞垂直分裂,产生有丝分裂成肌细胞和真皮。为了研究纺锤体取向是否影响命运分离,我们通过干扰 LGN 功能或过表达 inscuteable 使早期平面分裂随机化和/或转变为垂直取向。来自单个转染细胞的克隆表现出混合皮肌节/肌节祖细胞的比例增加,而在两个区域中“相似”的子细胞比例降低。晚期上皮中 LGN 或 Gαi1 功能的丧失使本来垂直的有丝分裂随机化,并有利于肌肉发育,而不利于真皮形成。因此,早期依赖于 LGN 的平面分裂对于将祖细胞正确分配到皮肌节或肌节中是必需的,而晚期垂直分裂对于肌肉和真皮产生之间的正常平衡是必需的。