Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109-2200, USA.
Department of Internal Medicine, Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, MI 48109-2200, USA.
Dev Cell. 2018 Jul 16;46(2):173-188.e3. doi: 10.1016/j.devcel.2018.06.011.
The early midgut undergoes intensive elongation, but the underlying cellular and molecular mechanisms are unknown. The early midgut epithelium is pseudostratified, and its nuclei travel between apical and basal surfaces in concert with cell cycle. Using 3D confocal imaging and 2D live imaging, we profiled behaviors of individual dividing cells. As nuclei migrate apically for mitosis, cells maintain a basal process (BP), which splits but is inherited by only one daughter. After mitosis, some daughters directly use the inherited BP as a "conduit" to transport the nucleus basally, while >50% of daughters generate a new basal filopodium and use it as a path to return the nucleus. Post-mitotic filopodial "pathfinding" is guided by mesenchymal WNT5A. Without WNT5A, some cells fail to tether basally and undergo apoptosis, leading to a shortened midgut. Thus, these studies reveal previously unrecognized strategies for efficient post-mitotic nuclear trafficking, which is critical for early midgut elongation.
早期中肠经历了剧烈的伸长,但潜在的细胞和分子机制尚不清楚。早期中肠上皮呈假复层,其核与细胞周期一起在顶端和基底表面之间迁移。通过使用 3D 共聚焦成像和 2D 活体成像,我们对单个分裂细胞的行为进行了分析。随着核为有丝分裂而向顶端迁移,细胞维持一个基底突起(BP),该突起分裂,但仅由一个子细胞继承。有丝分裂后,一些子细胞直接使用继承的 BP 作为将核基底运输的“导管”,而超过 50%的子细胞产生新的基底丝状伪足并将其用作返回核的路径。有丝分裂后丝状伪足的“寻路”由间质 WNT5A 指导。没有 WNT5A,一些细胞无法基底附着并发生凋亡,导致中肠缩短。因此,这些研究揭示了以前未被识别的高效有丝分裂后核运输策略,这对早期中肠伸长至关重要。