Centre for Organismal Studies, Heidelberg University, Heidelberg 69120, Germany.
Heidelberg Biosciences International Graduate School, Heidelberg 69120, Germany.
Development. 2021 Apr 1;148(7). doi: 10.1242/dev.199133. Epub 2021 Apr 15.
How the body and organs balance their relative growth is of key importance for coordinating size and function. This is of particular relevance in organisms, which continue to grow over their entire life span. We addressed this issue in the neuroretina of medaka fish (Oryzias latipes), a well-studied system with which to address vertebrate organ growth. We reveal that a central growth regulator, Igf1 receptor (Igf1r), is necessary and sufficient for proliferation control in the postembryonic retinal stem cell niche: the ciliary marginal zone (CMZ). Targeted activation of Igf1r signaling in the CMZ uncouples neuroretina growth from body size control, and we demonstrate that Igf1r operates on progenitor cells, stimulating their proliferation. Activation of Igf1r signaling increases retinal size while preserving its structural integrity, revealing a modular organization in which progenitor differentiation and neurogenesis are self-organized and highly regulated. Our findings position Igf signaling as a key module for controlling retinal size and composition, with important evolutionary implications.
身体和器官如何平衡其相对生长对于协调大小和功能至关重要。这在整个生命周期都在继续生长的生物体中尤为重要。我们在鱼类（斑马鱼）的神经视网膜中解决了这个问题，该系统是研究脊椎动物器官生长的一个很好的模型。我们揭示了一个中央生长调节剂，胰岛素样生长因子 1 受体（Igf1r），对于胚胎后视网膜干细胞巢，即纤毛缘区（CMZ）的增殖控制是必需和充分的。在 CMZ 中靶向激活 Igf1r 信号会使神经视网膜的生长与身体大小的控制脱钩，我们证明 Igf1r 作用于祖细胞，刺激它们的增殖。激活 Igf1r 信号会增加视网膜的大小，同时保持其结构完整性，揭示了一种模块化组织，其中祖细胞的分化和神经发生是自我组织和高度调控的。我们的发现将 Igf 信号定位为控制视网膜大小和组成的关键模块，具有重要的进化意义。
