Abstract
ABSTRACTHow 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.
Highlights
During embryonic development and postembryonic life of multicellular organisms, the proportions of overall body and organ size are actively controlled, being increased or decreased in a species-specific manner
We find igf1ra, igf2 and insrb expressed in the ciliary marginal zone (CMZ), and in specific layers of the differentiated retina (Fig. S1)
Single cells in the progenitor domain of the CMZ as well as Müller glia (MG) cells in the inner nuclear layer (INL) in the differentiated part of the retina were positive for pIgf1r (Fig. 1B)
Summary
During embryonic development and postembryonic life of multicellular organisms, the proportions of overall body and organ size are actively controlled, being increased or decreased in a species-specific manner. Scaling of overall body and organ size is known to be regulated by systemic signals, which couple nutritional status to growth (Andersen et al, 2013). Differential growth of organs can be the result of altered sensitivity to systemic signaling (Tang et al, 2011) as well as of variant intrinsic signaling in the respective organ (Bosch et al, 2017; Twitty and Schwind, 1931). Different eye dimensions of teleost species have been shown to be of functional relevance, as visual acuity is notably correlated with eye size (Caves et al, 2017). Vision and in particular retinal size and relative cell type composition are highly relevant for habitat-specific function and for speciation.
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