Department of Ophthalmology, Center for Vision Research, and SUNY Eye Institute, SUNY Upstate Medical University, Syracuse, New York, United States of America.
PLoS One. 2011;6(7):e22278. doi: 10.1371/journal.pone.0022278. Epub 2011 Jul 19.
During animal development, accurate control of tissue specification and growth are critical to generate organisms of reproducible shape and size. The eye-antennal disc epithelium of Drosophila is a powerful model system to identify the signaling pathway and transcription factors that mediate and coordinate these processes. We show here that the Yorkie (Yki) pathway plays a major role in tissue specification within the developing fly eye disc epithelium at a time when organ primordia and regional identity domains are specified. RNAi-mediated inactivation of Yki, or its partner Scalloped (Sd), or increased activity of the upstream negative regulators of Yki cause a dramatic reorganization of the eye disc fate map leading to specification of the entire disc epithelium into retina. On the contrary, constitutive expression of Yki suppresses eye formation in a Sd-dependent fashion. We also show that knockdown of the transcription factor Homothorax (Hth), known to partner Yki in some developmental contexts, also induces an ectopic retina domain, that Yki and Scalloped regulate Hth expression, and that the gain-of-function activity of Yki is partially dependent on Hth. Our results support a critical role for Yki- and its partners Sd and Hth--in shaping the fate map of the eye epithelium independently of its universal role as a regulator of proliferation and survival.
在动物发育过程中，精确控制组织特化和生长对于生成具有可重复形状和大小的生物体至关重要。果蝇的眼-触角盘上皮组织是一个强大的模型系统，可以识别介导和协调这些过程的信号通路和转录因子。我们在这里表明，在器官原基和区域身份域指定的时期，Yorkie（Yki）途径在发育中的果蝇眼盘上皮组织的组织特化中发挥主要作用。通过 RNAi 介导的 Yki 失活、其伴侣 Scalloped（Sd）或其上游 Yki 的负调控因子的活性增加，会导致眼盘命运图谱的剧烈重组，导致整个盘上皮组织特化为视网膜。相反，Yki 的组成型表达以 Sd 依赖的方式抑制眼睛的形成。我们还表明，转录因子 Homothorax（Hth）的敲低，已知在某些发育情况下与 Yki 合作，也会诱导异位视网膜区域，Yki 和 Sd 调节 Hth 的表达，并且 Yki 的功能获得活性部分依赖于 Hth。我们的结果支持 Yki 及其伴侣 Sd 和 Hth 在独立于其作为增殖和存活调节剂的普遍作用的情况下塑造眼上皮组织命运图谱方面的关键作用。
