Merkel Matthias, Sagner Andreas, Gruber Franz Sebastian, Etournay Raphael, Blasse Corinna, Myers Eugene, Eaton Suzanne, Jülicher Frank
Max Planck Institute for the Physics of Complex Systems, Nöthnitzer Strasse 38, 01187 Dresden, Germany.
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01309 Dresden, Germany.
Curr Biol. 2014 Sep 22;24(18):2111-2123. doi: 10.1016/j.cub.2014.08.005. Epub 2014 Sep 4.
The conserved Fat and Core planar cell polarity (PCP) pathways work together to specify tissue-wide orientation of hairs and ridges in the Drosophila wing. Their components form intracellularly polarized complexes at adherens junctions that couple the polarity of adjacent cells and form global patterns. How Fat and Core PCP systems interact is not understood. Some studies suggest that Fat PCP directly orients patterns formed by Core PCP components. Others implicate oriented tissue remodeling in specifying Core PCP patterns.
We use genetics, quantitative image analysis, and physical modeling to study Fat and Core PCP interactions during wing development. We show their patterns change during morphogenesis, undergoing phases of coupling and uncoupling that are regulated by antagonistic Core PCP protein isoforms Prickle and Spiny-legs. Evolving patterns of Core PCP are hysteretic: the early Core PCP pattern is modified by tissue flows and then by coupling to Fat PCP, producing sequential patterns that guide hairs and then ridges. Our data quantitatively account for altered hair and ridge polarity patterns in PCP mutants. Premature coupling between Fat and Core PCP explains altered polarity patterns in pk mutants. In other Core PCP mutants, hair polarity patterns are guided directly by Fat PCP. When both systems fail, hairs still align locally and obey signals associated with veins.
Temporally regulated coupling between the Fat and Core PCP systems enables a single tissue to develop sequential polarity patterns that orient distinct morphological structures.
保守的Fat和核心平面细胞极性（PCP）通路共同作用，决定果蝇翅膀中毛发和脊在整个组织范围内的方向。它们的组成部分在黏着连接处形成细胞内极化复合物，这些复合物将相邻细胞的极性耦合起来并形成全局模式。目前尚不清楚Fat和核心PCP系统是如何相互作用的。一些研究表明，Fat PCP直接决定由核心PCP组件形成的模式的方向。另一些研究则暗示定向组织重塑在确定核心PCP模式中起作用。
我们利用遗传学、定量图像分析和物理建模来研究翅膀发育过程中Fat和核心PCP的相互作用。我们发现它们的模式在形态发生过程中发生变化，经历了由拮抗的核心PCP蛋白异构体Prickle和Spiny-legs调节的耦合和解耦合阶段。核心PCP不断演变的模式具有滞后性：早期的核心PCP模式先被组织流动改变，然后通过与Fat PCP耦合而改变，产生引导毛发然后是脊的连续模式。我们的数据定量解释了PCP突变体中毛发和脊极性模式的改变。Fat和核心PCP之间的过早耦合解释了pk突变体中极性模式的改变。在其他核心PCP突变体中，毛发极性模式直接由Fat PCP引导。当两个系统都失效时，毛发仍然局部排列并遵循与静脉相关的信号。
Fat和核心PCP系统之间受时间调节的耦合使单个组织能够形成连续的极性模式，从而确定不同的形态结构的方向。
