Adler P N, Krasnow R E, Liu J
Biology Department, University of Virginia, Charlottesville, Virginia 22903, USA.
Curr Biol. 1997 Dec 1;7(12):940-9. doi: 10.1016/s0960-9822(06)00413-1.
The frizzled (fz) gene of Drosophila encodes the founding member of the large family of receptors for the Wnt family of signaling molecules. It was originally studied in the adult epidermis, where it plays a key role in the generation of tissue polarity. Mutations in components of the fz signal transduction pathway disrupt tissue polarity; on the wing, hairs normally point distally but their polarity is altered by these mutations.
We devised a method to induce a gradient of fz expression with the highest levels near the distal wing tip. The result was a large area of proximally pointing hairs in this region. This reversal of polarity was seen when fz expression was induced just before the start of hair morphogenesis when polarity is established, suggesting that the gradient of Fz protein acted fairly directly to reverse hair polarity. A similar induction of the dishevelled (dsh) gene, which acts cell autonomously and functions downstream of fz in the generation of tissue polarity, resulted in a distinct tissue polarity phenotype, but no reversal of polarity; this argues that fz signaling was required for polarity reversal. Furthermore, the finding that functional dsh was required for the reversal of polarity argues that the reversal requires normal fz signal transduction.
The data suggest that cells sense the level of Fz protein on neighboring cells and use this information in order to polarize themselves. A polarizing signal is transmitted from cells with higher Fz levels to cells with lower levels. Our observations enable us to propose a general mechanism to explain how Wnts polarize target cells.
果蝇的卷曲（fz）基因编码Wnt信号分子家族众多受体中的首个成员。最初它是在成年表皮中被研究的，在那里它在组织极性的产生中起关键作用。fz信号转导途径成分的突变会破坏组织极性；在翅膀上，毛通常指向远端，但这些突变会改变它们的极性。
我们设计了一种方法来诱导fz表达梯度，在翅膀远端尖端附近表达水平最高。结果是在该区域出现了一大片指向近端的毛。当在毛形态发生开始前（即极性确立时）诱导fz表达时，就会看到这种极性反转，这表明Fz蛋白梯度相当直接地作用于反转毛的极性。对蓬乱（dsh）基因进行类似诱导，该基因在组织极性产生过程中自主发挥作用且在fz下游起作用，会导致一种独特的组织极性表型，但不会出现极性反转；这表明极性反转需要fz信号传导。此外，极性反转需要功能性dsh这一发现表明，这种反转需要正常的fz信号转导。
数据表明细胞感知相邻细胞上Fz蛋白的水平，并利用这些信息使自身极化。极化信号从Fz水平较高的细胞传递到水平较低的细胞。我们的观察结果使我们能够提出一种通用机制来解释Wnts如何使靶细胞极化。
