Colon Cryptogenesis: Asymmetric Budding
Colon Cryptogenesis: Asymmetric Budding
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DOI：
10.1371/journal.pone.0078519
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发表时间：
2013-10-21
期刊：
影响因子：
3.7
通讯作者：
Burgess, Antony W.
中科院分区：
文献类型：
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作者：
Tan, Chin Wee;Hirokawa, Yumiko;Burgess, Antony W.
隐窝形成的过程和Wnt和细胞-细胞粘附信号在隐发生中的作用还没有很好的描述，但对于理解正常和癌症结肠隐窝生物学是重要的。一个定量的三维显微镜和图像分析技术被用来研究与隐窝形成的频率，形态和分子形貌。测量沿着结肠揭示了隐窝形成的细节和一些关键的基本生化信号调节正常结肠生物学。我们的测量结果显示，一个不对称的地穴出芽过程，相反，以前报道的对称分裂的地穴。三维免疫荧光分析揭示了不同隐窝人群中E-钙粘蛋白和β-连环蛋白亚细胞分布的异质性。这种异质性也被发现在不对称的发芽隐窝。在从正常结肠粘膜分离的隐窝中观察到单一隐窝形成（即，没有从一个亲本隐窝形成多个新的隐窝），这提示了防止异常隐窝产生的单一约束机制。提出的技术提高了我们对隐生的理解，并表明当Wnt信号传导受到干扰时，会发生过量的结肠隐窝形成（例如，G.通过截短腺瘤性结肠息肉病，APC蛋白）。
The process of crypt formation and the roles of Wnt and cell-cell adhesion signaling in cryptogenesis are not well described; but are important to the understanding of both normal and cancer colon crypt biology. A quantitative 3D-microscopy and image analysis technique is used to study the frequency, morphology and molecular topography associated with crypt formation. Measurements along the colon reveal the details of crypt formation and some key underlying biochemical signals regulating normal colon biology. Our measurements revealed an asymmetrical crypt budding process, contrary to the previously reported symmetrical fission of crypts. 3D immunofluorescence analyses reveals heterogeneity in the subcellular distribution of E-cadherin and beta-catenin in distinct crypt populations. This heterogeneity was also found in asymmetrical budding crypts. Singular crypt formation (i.e. no multiple new crypts forming from one parent crypt) were observed in crypts isolated from the normal colon mucosa, suggestive of a singular constraint mechanism to prevent aberrant crypt production. The technique presented improves our understanding of cryptogenesis and suggests that excess colon crypt formation occurs when Wnt signaling is perturbed (e. g. by truncation of adenomatous polyposis coli, APC protein) in most colon cancers.