A junction-dependent mechanism drives murine mammary cell intercalation for ductal elongation.
A junction-dependent mechanism drives murine mammary cell intercalation for ductal elongation.
复制标题
连接依赖性机制驱动小鼠乳腺细胞嵌入以实现导管伸长。
DOI：
10.1016/j.devcel.2023.04.009
复制
发表时间：
2023
影响因子：
11.8
通讯作者：
Macara,IanG
中科院分区：
文献类型：
--
作者：
Pfannenstein,Alexander;Macara,IanG
乳腺的腔上皮组织成单层;然而，它起源于发育过程中的多层末端芽（TEB）。虽然细胞凋亡为导管腔的空化提供了一个合理的机制，但它不能解释TEB后面的导管伸长。小鼠中的空间计算表明，大多数TEB细胞整合到最外层腔层中以产生延伸。我们开发了一种定量细胞培养试验，模型嵌入上皮单层。我们发现紧密连接蛋白在这个过程中起着关键作用。ZO-1斑点在新的细胞界面处形成，并随着嵌入的进行而分解成新的边界。删除ZO-1抑制了培养物和通过导管内注射移植到乳腺中的细胞中的嵌入。在界面处的细胞骨架重排对于嵌入是至关重要的。这些数据确定了乳腺发育所需的管腔细胞重排，并提出了细胞整合到现有单层中的机制。
The luminal epithelium of the mammary gland is organized into monolayers; however, it originates from multilayered terminal end buds (TEBs) during development. Although apoptosis provides a plausible mechanism for cavitation of the ductal lumen, it doesn't account for ductal elongation behind TEBs. Spatial calculations in mice suggest that most TEB cells integrate into the outermost luminal layer to generate elongation. We developed a quantitative cell culture assay that models intercalation into epithelial monolayers. We found that tight junction proteins play a key role in this process. ZO-1 puncta form at the new cellular interface and resolve into a new boundary as intercalation proceeds. Deleting ZO-1 suppresses intercalation both in culture and in cells transplanted into mammary glands via intraductal injection. Cytoskeletal rearrangements at the interface are critical for intercalation. These data identify luminal cell rearrangements necessary for mammary development and suggest a mechanism for integration of cells into an existing monolayer.