Self-organization of engineered epithelial tubules by differential cellular motility
Self-organization of engineered epithelial tubules by differential cellular motility
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DOI：
10.1073/pnas.0901269106
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发表时间：
2009-09-01
影响因子：
11.1
通讯作者：
Nelson, Celeste M.
中科院分区：
文献类型：
--
作者：
Mori, Hidetoshi;Gjorevski, Nikolce;Nelson, Celeste M.
发育中组织的图案化由多种机制产生，包括细胞形状变化、细胞增殖以及根据不同的内聚力或张力进行细胞分选。在这里，我们发现细胞运动的差异也可能导致组织内的细胞分选。使用镶嵌工程乳腺上皮小管，我们发现细胞根据膜锚定胶原酶基质金属蛋白酶（MMP）-14 的表达水平进行分类。这些重排独立于 MMP14 的催化活性，但绝对需要血红素结合蛋白结构域。我们描述了 MMP14 通过 Rho 激酶下游的信号级联，该级联允许细胞在模型组织内进行分类。 MMP14 表达增强了细胞速度和持久时间，但分选只需要后者运动参数。这些结果表明，差异方向持久性可以在模型发育组织内产生模式。
Patterning of developing tissues arises from a number of mechanisms, including cell shape change, cell proliferation, and cell sorting from differential cohesion or tension. Here, we reveal that differences in cell motility can also lead to cell sorting within tissues. Using mosaic engineered mammary epithelial tubules, we found that cells sorted depending on their expression level of the membrane-anchored collagenase matrix metalloproteinase (MMP)-14. These rearrangements were independent of the catalytic activity of MMP14 but absolutely required the hemopexin domain. We describe a signaling cascade downstream of MMP14 through Rho kinase that allows cells to sort within the model tissues. Cell speed and persistence time were enhanced by MMP14 expression, but only the latter motility parameter was required for sorting. These results indicate that differential directional persistence can give rise to patterns within model developing tissues.