MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, University College London, Gower Street, London, WC1E 6BT, UK.
Development. 2012 Sep;139(18):3432-41. doi: 10.1242/dev.080762. Epub 2012 Aug 8.
Morphogenesis of epithelial tissues relies on the interplay between cell division, differentiation and regulated changes in cell shape, intercalation and sorting. These processes are often studied individually in relatively simple epithelia that lack the complexity found during organogenesis when these processes might all coexist simultaneously. To address this issue, we are making use of the developing fly retinal neuroepithelium. Retinal morphogenesis relies on a coordinated sequence of interdependent morphogenetic events that includes apical cell constriction, localized alignment of groups of cells and ommatidia morphogenesis coupled to neurogenesis. Here, we use live imaging to document the sequence of adherens junction (AJ) remodelling events required to generate the fly ommatidium. In this context, we demonstrate that the kinases Rok and Drak function redundantly during Myosin II-dependent cell constriction, subsequent multicellular alignment and AJ remodelling. In addition, we show that early multicellular patterning characterized by cell alignment is promoted by the conserved transcription factor Atonal (Ato). Further ommatidium patterning requires the epidermal growth factor receptor (EGFR) signalling pathway, which transcriptionally governs rok- and Drak-dependent AJ remodelling while also promoting neurogenesis. In conclusion, our work reveals an important role for Drak in regulating AJ remodelling during retinal morphogenesis. It also sheds new light on the interplay between Ato, EGFR-dependent transcription and AJ remodelling in a system in which neurogenesis is coupled with cell shape changes and regulated steps of cell intercalation.
上皮组织的形态发生依赖于细胞分裂、分化和细胞形状、内插和分选的调节变化之间的相互作用。这些过程通常在相对简单的上皮组织中单独研究，这些上皮组织缺乏器官发生过程中同时存在的复杂性。为了解决这个问题，我们正在利用发育中的果蝇视网膜神经上皮。视网膜形态发生依赖于一系列协调的、相互依存的形态发生事件，包括顶端细胞收缩、细胞群的局部排列以及与神经发生偶联的小眼形态发生。在这里，我们使用活细胞成像来记录生成果蝇小眼所需的黏着连接（AJ）重塑事件的顺序。在这种情况下，我们证明了激酶 Rok 和 Drak 在肌球蛋白 II 依赖性细胞收缩、随后的多细胞排列和 AJ 重塑过程中冗余。此外，我们还表明，以细胞排列为特征的早期多细胞模式形成是由保守的转录因子 Atonal (Ato) 促进的。进一步的小眼模式形成需要表皮生长因子受体 (EGFR) 信号通路，该通路转录调控 rok 和 Drak 依赖性 AJ 重塑，同时也促进神经发生。总之，我们的工作揭示了 Drak 在调控视网膜形态发生过程中的 AJ 重塑中的重要作用。它还揭示了 Ato、EGFR 依赖性转录和 AJ 重塑之间的相互作用，在这个系统中，神经发生与细胞形状变化和细胞内插的调节步骤偶联。
