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Integrin-Mediated Focal Anchorage Drives Epithelial Zippering during Mouse Neural Tube Closure.
Developmental Cell ( IF 10.7 ) Pub Date : 2020-02-10 , DOI: 10.1016/j.devcel.2020.01.012 Matteo A Molè 1 , Gabriel L Galea 2 , Ana Rolo 2 , Antonia Weberling 3 , Oleksandr Nychyk 4 , Sandra C De Castro 2 , Dawn Savery 2 , Reinhard Fässler 5 , Patricia Ybot-González 6 , Nicholas D E Greene 2 , Andrew J Copp 2
Developmental Cell ( IF 10.7 ) Pub Date : 2020-02-10 , DOI: 10.1016/j.devcel.2020.01.012 Matteo A Molè 1 , Gabriel L Galea 2 , Ana Rolo 2 , Antonia Weberling 3 , Oleksandr Nychyk 4 , Sandra C De Castro 2 , Dawn Savery 2 , Reinhard Fässler 5 , Patricia Ybot-González 6 , Nicholas D E Greene 2 , Andrew J Copp 2
Affiliation
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Epithelial fusion is a key process of morphogenesis by which tissue connectivity is established between adjacent epithelial sheets. A striking and poorly understood feature of this process is "zippering," whereby a fusion point moves directionally along an organ rudiment. Here, we uncover the molecular mechanism underlying zippering during mouse spinal neural tube closure. Fusion is initiated via local activation of integrin β1 and focal anchorage of surface ectoderm cells to a shared point of fibronectin-rich basement membrane, where the neural folds first contact each other. Surface ectoderm cells undergo proximal junction shortening, establishing a transitory semi-rosette-like structure at the zippering point that promotes juxtaposition of cells across the midline enabling fusion propagation. Tissue-specific ablation of integrin β1 abolishes the semi-rosette formation, preventing zippering and causing spina bifida. We propose integrin-mediated anchorage as an evolutionarily conserved mechanism of general relevance for zippering closure of epithelial gaps whose disturbance can produce clinically important birth defects.
中文翻译：
整合素介导的局灶性锚定在小鼠神经管闭合过程中驱动上皮拉链。
上皮融合是形态发生的关键过程，通过该过程在相邻上皮片之间建立组织连接性。这一过程的一个显着且鲜为人知的特征是“拉链”，即融合点沿着器官雏形定向移动。在这里，我们揭示了小鼠脊髓神经管闭合过程中拉链的分子机制。融合是通过整合素 β1 的局部激活和表面外胚层细胞局部锚定到富含纤连蛋白的基底膜的共享点来启动的，神经褶皱首先在此处相互接触。表面外胚层细胞经历近端连接缩短，在拉链点建立暂时的半玫瑰花状结构，促进细胞穿过中线并置，从而实现融合传播。整合素 β1 的组织特异性消融消除了半玫瑰花结的形成，防止拉锁并引起脊柱裂。我们提出整合素介导的锚定作为一种进化上保守的机制，与上皮间隙的拉链闭合普遍相关，其干扰可能产生临床上重要的出生缺陷。
更新日期：2020-02-20
中文翻译：
整合素介导的局灶性锚定在小鼠神经管闭合过程中驱动上皮拉链。
上皮融合是形态发生的关键过程，通过该过程在相邻上皮片之间建立组织连接性。这一过程的一个显着且鲜为人知的特征是“拉链”，即融合点沿着器官雏形定向移动。在这里，我们揭示了小鼠脊髓神经管闭合过程中拉链的分子机制。融合是通过整合素 β1 的局部激活和表面外胚层细胞局部锚定到富含纤连蛋白的基底膜的共享点来启动的，神经褶皱首先在此处相互接触。表面外胚层细胞经历近端连接缩短，在拉链点建立暂时的半玫瑰花状结构，促进细胞穿过中线并置，从而实现融合传播。整合素 β1 的组织特异性消融消除了半玫瑰花结的形成，防止拉锁并引起脊柱裂。我们提出整合素介导的锚定作为一种进化上保守的机制，与上皮间隙的拉链闭合普遍相关，其干扰可能产生临床上重要的出生缺陷。
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