Direct activation of Shroom3 transcription by Pitx proteins drives epithelial morphogenesis in the developing gut
Direct activation of Shroom3 transcription by Pitx proteins drives epithelial morphogenesis in the developing gut
复制标题
DOI：
10.1242/dev.044610
复制
发表时间：
2010-04-15
期刊：
影响因子：
4.6
通讯作者：
Wallingford, John B.
中科院分区：
文献类型：
--
作者：
Chung, Mei-I;Nascone-Yoder, Nanette M.;Wallingford, John B.
个别细胞形状的改变是上皮形态发生所必需的。在果蝇中出现了上皮细胞形状改变的转录网络，但在脊椎动物中，这一区域在很大程度上仍未被探索。这种区别很重要，因为到目前为止，果蝇细胞形状变化的关键下游效应因子似乎并不保守。相反，Shroom3已经成为脊椎动物上皮形态发生的中心效应器，驱动基于肌动蛋白和微管的细胞形状变化。到目前为止，Shroom3的形态发生作用只在神经上皮细胞中被探索过，因此该基因的广泛表达提出了两个重要的问题：非神经组织对Shroom3的要求是什么，以及什么因素控制Shroom3的转录？在这里，我们在非洲爪哇表明，Shroom3对于脊椎动物发育中的肠道细胞形状变化和形态发生是必不可少的，并且Shroom3在肠道中的转录需要Pitx1转录因子。此外，我们发现Pitx蛋白直接激活Shroom3的转录，我们在Shroom3上游的基因组DNA中发现了Pitx反应的调控元件。最后，我们证明了PITX蛋白的异位表达足以诱导Shroom3依赖的细胞骨架重组和上皮细胞形状的改变。这些数据表明Shroom3在形态发生中的要求有了新的广度，也为Pitx转录因子在形态发生中的作用提供了细胞生物学基础。更广泛地说，这些结果为破译脊椎动物发育中上皮细胞形状变化背后的转录网络提供了基础。
Individual cell shape changes are essential for epithelial morphogenesis. A transcriptional network for epithelial cell shape change is emerging in Drosophila, but this area remains largely unexplored in vertebrates. The distinction is important as so far, key downstream effectors of cell shape change in Drosophila appear not to be conserved. Rather, Shroom3 has emerged as a central effector of epithelial morphogenesis in vertebrates, driving both actin-and microtubule-based cell shape changes. To date, the morphogenetic role of Shroom3 has been explored only in the neural epithelium, so the broad expression of this gene raises two important questions: what are the requirements for Shroom3 in non-neural tissues and what factors control Shroom3 transcription? Here, we show in Xenopus that Shroom3 is essential for cell shape changes and morphogenesis in the developing vertebrate gut and that Shroom3 transcription in the gut requires the Pitx1 transcription factor. Moreover, we show that Pitx proteins directly activate Shroom3 transcription, and we identify Pitx-responsive regulatory elements in the genomic DNA upstream of Shroom3. Finally, we show that ectopic expression of Pitx proteins is sufficient to induce Shroom3-dependent cytoskeletal reorganization and epithelial cell shape change. These data demonstrate new breadth to the requirements for Shroom3 in morphogenesis, and they also provide a cell-biological basis for the role of Pitx transcription factors in morphogenesis. More generally, these results provide a foundation for deciphering the transcriptional network that underlies epithelial cell shape change in developing vertebrates.