Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, United States of America.
PLoS Genet. 2011 Aug;7(8):e1002226. doi: 10.1371/journal.pgen.1002226. Epub 2011 Aug 11.
Optic cups are a structural feature of diverse eyes, from simple pit eyes to camera eyes of vertebrates and cephalopods. We used the planarian prototypic eye as a model to study the genetic control of optic cup formation and regeneration. We identified two genes encoding transcription factors, sp6-9 and dlx, that were expressed in the eye specifically in the optic cup and not the photoreceptor neurons. RNAi of these genes prevented formation of visible optic cups during regeneration. Planarian regeneration requires an adult proliferative cell population with stem cell-like properties called the neoblasts. We found that optic cup formation occurred only after migration of progressively differentiating progenitor cells from the neoblast population. The eye regeneration defect caused by dlx and sp6-9 RNAi can be explained by a failure to generate these early optic cup progenitors. Dlx and Sp6-9 genes function as a module during the development of diverse animal appendages, including vertebrate and insect limbs. Our work reveals a novel function for this gene pair in the development of a fundamental eye component, and it utilizes these genes to demonstrate a mechanism for total organ regeneration in which extensive cell movement separates new cell specification from organ morphogenesis.
视杯是多种眼睛的结构特征，从简单的眼窝到脊椎动物和头足类动物的摄像头眼。我们使用扁形虫原型眼作为模型，研究视杯形成和再生的遗传控制。我们鉴定了两个编码转录因子 sp6-9 和 dlx 的基因，这些基因在眼睛中特异性地在视杯中表达，而不在光感受器神经元中表达。这些基因的 RNAi 阻止了再生过程中可见视杯的形成。扁形虫再生需要具有成体增殖细胞特性的细胞群体，称为成体干细胞样细胞，即 neoblasts。我们发现，只有当来自 neoblast 群体的逐渐分化的祖细胞迁移时，视杯的形成才会发生。dlx 和 sp6-9 RNAi 引起的眼睛再生缺陷可以通过未能产生这些早期视杯祖细胞来解释。Dlx 和 Sp6-9 基因在包括脊椎动物和昆虫肢体在内的各种动物附肢的发育中作为一个模块发挥作用。我们的工作揭示了这对基因在基本眼睛成分发育中的新功能，并利用这些基因证明了一种用于总器官再生的机制，其中广泛的细胞运动将新的细胞特化与器官形态发生分开。
