Yap A S, Manley S W
Department of Physiology and Pharmacology, The University of Queensland, St. Lucia, Brisbane, Australia.
Cell Motil Cytoskeleton. 2001 Mar;48(3):201-12. doi: 10.1002/1097-0169(200103)48:3<201::AID-CM1009>3.0.CO;2-C.
In this study, we examined the contribution of microtubules to epithelial morphogenesis in primary thyroid cell cultures. Thyroid follicles consist of a single layer of polarized epithelial cells surrounding a closed compartment, the follicular lumen. Freshly isolated porcine thyroid cells aggregate and reorganize to form follicles when grown in primary cultures. Follicular reorganization is principally a morphogenetic process that entails the assembly of biochemically distinct apical and basolateral membrane domains, delimited by tight junctions. The establishment of cell surface polarity during folliculogenesis coincided with the polarized redistribution of microtubules, predominantly in the developing apical poles of cells. Disruption of microtubule integrity using either colchicine or nocodazole caused loss of defined apical membrane domains, tight junctions and follicular lumina. Apical membrane and tight junction markers became randomly distributed at the outer surfaces of aggregates. In contrast, the basolateral surface markers, E-cadherin and Na(+),K(+)-ATPase, remained correctly localized at sites of cell-cell contact and at the free surfaces of cell aggregates. These findings demonstrate that microtubules play a necessary role in thyroid epithelial morphogenesis. Specifically, microtubules are essential to preserve the correct localization of apical membrane components within enclosed cellular aggregates, a situation that is also likely to pertain where lumina must be formed from solid aggregates of epithelial precursors.
在本研究中，我们检测了微管在原代甲状腺细胞培养中对上皮形态发生的作用。甲状腺滤泡由围绕封闭腔室（滤泡腔）的单层极化上皮细胞组成。新鲜分离的猪甲状腺细胞在原代培养中生长时会聚集并重新组织形成滤泡。滤泡重组主要是一个形态发生过程，需要组装由紧密连接界定的生化性质不同的顶端和基底外侧膜结构域。在滤泡形成过程中细胞表面极性的建立与微管的极化重新分布同时发生，主要分布在细胞发育中的顶端极。使用秋水仙碱或诺考达唑破坏微管完整性会导致明确的顶端膜结构域、紧密连接和滤泡腔的丧失。顶端膜和紧密连接标记物在聚集体的外表面随机分布。相反，基底外侧表面标记物E-钙黏蛋白和钠钾ATP酶仍正确定位在细胞-细胞接触部位和细胞聚集体的自由表面。这些发现表明微管在甲状腺上皮形态发生中起必要作用。具体而言，微管对于维持封闭细胞聚集体内顶端膜成分的正确定位至关重要，这种情况也可能适用于上皮前体的固体聚集体必须形成腔室的情况。
