Wnt signaling is one of the major signaling pathways that regulate cell differentiation, tissue patterning and stem cell homeostasis and its dysfunction causes many human diseases, such as cancer. It is of tremendous interests to understand how Wnt signaling is regulated in a precise manner both temporally and spatially. Naked cuticle (Nkd) acts as a negative-feedback inhibitor for Wingless (Wg, a fly Wnt) signaling in Drosophila embryonic development. However, the role of Nkd remains controversial in later fly development, particularly on the canonical Wg pathway. In the present study, we show that nkd is essential for wing pattern formation, such that both gain and loss of nkd result in the disruption of Wg target expression in larvae stage and abnormal adult wing morphologies. Furthermore, we demonstrate that a thirty amino acid fragment in Nkd, identified previously in Wharton lab, is critical for the canonical Wg signaling, but is dispensable for Wg/planar cell polarity pathway. Putting aside the pleiotropic nature of nkd function, i.e. its role in the Decapentaplegic signaling, we conclude that Nkd universally inhibits the canonical Wg pathway across a life span of Drosophila development.

Wnt 信号是调节细胞分化、组织模式和干细胞稳态的主要信号通路之一，其功能障碍会导致许多人类疾病，如癌症。了解 Wnt 信号如何在时间和空间上以精确的方式进行调节具有极大的兴趣。裸表皮 (Nkd) 在果蝇胚胎发育中充当 Wingless (Wg，苍蝇 Wnt) 信号传导的负反馈抑制剂。然而，Nkd 在后来的苍蝇发育中的作用仍然存在争议，特别是在规范 Wg 通路上。在本研究中，我们表明nkd对于翼型形成至关重要，因此nkd 的获得和损失导致幼虫阶段 Wg 目标表达的破坏和成虫翅膀形态的异常。此外，我们证明了 Nkd 中的 30 个氨基酸片段，之前在沃顿实验室中发现，对于典型的 Wg 信号传导至关重要，但对于 Wg/平面细胞极性通路是可有可无的。撇开nkd功能的多效性，即它在十五位麻痹信号中的作用，我们得出结论，Nkd 在果蝇发育的整个生命周期中普遍抑制经典 Wg 通路。