Identification of novel ciliogenesis factors using a new in vivo model for mucociliary epithelial development
Identification of novel ciliogenesis factors using a new in vivo model for mucociliary epithelial development
复制标题
DOI：
10.1016/j.ydbio.2007.09.031
复制
发表时间：
2007-12-01
影响因子：
2.7
通讯作者：
Wallingford, John B.
中科院分区：
文献类型：
--
作者：
Hayes, Julie M.;Kim, Su Kyoung;Wallingford, John B.
纤毛黏液上皮由分泌黏液的杯状细胞和纤毛细胞组成，对许多器官的体内平衡至关重要。在这里，我们提出非洲爪蟾胚胎的纤毛表皮作为一个简单的模型系统，在体内分子研究粘液纤毛上皮的发育。使用基于原位杂交的方法，我们鉴定了许多在粘液分泌细胞或纤毛细胞中表达差异的基因。关注纤毛细胞中表达的基因，我们已经确定了新的候选纤毛发生因子，包括当前纤毛中不存在的一些因子。我们发现TTC25- gfp定位于纤毛基部和纤毛轴突，破坏TTC25的功能会破坏纤毛的发生。Mig12-GFP非常强烈地定位于纤毛的基部，这种结构的共聚焦成像可以简单地显示基体的平面极性，基体是极化纤毛跳动的基础。敲低Mig12会破坏纤毛的形成。最后，我们发现在爪蟾表皮中发现的纤毛发生因子在中线中是促进神经管闭合所必需的。这些结果进一步证明了神经管形态发生需要纤毛，并表明在表皮爪蟾中发现的基因在纤毛发生中发挥了广泛的作用。在此鉴定的基因组将为未来的研究提供基础，也可能有助于我们理解伴随哮喘等疾病的粘膜纤毛上皮病理变化。(C) 2007爱思唯尔公司版权所有。
Mucociliary epithelia are essential for homeostasis of many organs and consist of mucus-secreting goblet cells and ciliated cells. Here, we present the ciliated epidermis of Xenopus embryos as a facile model system for in vivo molecular studies of mucociliary epithelial development. Using an in situ hybridization-based approach, we identified numerous genes expressed differentially in mucus-secreting cells or in ciliated cells. Focusing on genes expressed in ciliated cells, we have identified new candidate ciliogenesis factors, including several not present in the current ciliome. We find that TTC25-GFP is localized to the base of cilia and to ciliary axonemes, and disruption of TTC25 function disrupts ciliogenesis. Mig12-GFP localizes very strongly to the base of cilia and confocal imaging of this construct allows for simple visualization of the planar polarity of basal bodies that underlies polarized ciliary beating. Knockdown of Mig12 disrupts ciliogenesis. Finally, we show that ciliogenesis factors identified in the Xenopus epidermis are required in the midline to facilitate neural tube closure. These results provide further evidence of a requirement for cilia in neural tube morphogenesis and suggest that genes identified in the Xenopus epidermis play broad roles in ciliogenesis. The suites of genes identified here will provide a foundation for future studies, and may also contribute to our understanding of pathological changes in mucociliary epithelia that accompany diseases such as asthma. (C) 2007 Elsevier Inc. All rights reserved.