2025-11-20 ニューヨーク大学(NYU)
<関連情報>
- https://www.nyu.edu/about/news-publications/news/2025/november/calcium-waves-flies-eyes.html
- https://www.science.org/doi/10.1126/science.ady5541
網膜カルシウム波はショウジョウバエの眼の均一な組織パターンを形成する Retinal calcium waves coordinate uniform tissue patterning of the Drosophila eye
Ben Jiwon Choi, Yen-Chung Chen, and Claude Desplan
Science Published:20 Nov 2025
DOI:https://doi.org/10.1126/science.ady5541
Editor’s summary
Achieving precise structural and functional specialization requires coordination between multiple cell types during the development of the central nervous system. Studying retinal morphogenesis in the developing eye of fruit flies (Drosophila melanogaster), Choi et al. identified spontaneous calcium waves originating from non-neuronal cells responsible for orchestrating tissue architecture in the developing nervous system (see the Perspective by Kumar). Initiation of these waves involved a receptor tyrosine kinase inducing phospholipase Cγ–mediated calcium release from the endoplasmic reticulum. After initiation, wave propagation followed a defined gap junction pathway across three distinct types of non-neuronal retinal cells. The results uncover a calcium-dependent mechanism in non-neuronal cells coordinating the development of the nervous system in Drosophila. —Mattia Maroso
Structured Abstract
INTRODUCTION
Precise neural function requires accurate tissue organization of multiple cell types. This is often achieved by synchronized waves of calcium activity that enable transient communication and coordination between cells during nervous system development. This evolutionarily conserved activity is observed in both vertebrate and invertebrate systems and occurs in neuronal as well as non-neuronal cells. Neuronal retinal waves in the mammalian eye are among the best-characterized examples, documented across species including the human fetal retina. These neurotransmission-mediated retinal waves play critical roles in refining synaptic connectivity and aligning sensory circuits between processing layers of the brain.
RATIONALE
Non-neuronal support cells such as glial and epithelial cells also exhibit robust calcium waves observed in multiple systems, including the retina. These waves, mediated by gap junction networks, coordinate cellular behaviors over large fields and have been implicated in cell proliferation and specification, although they can also occur at later stages of development. Whether non-neuronal calcium waves also contribute to tissue maturation remains unclear. Clarifying this role could reveal how these calcium waves coordinate neuronal wiring to shape mature tissue architecture of neural tissues.
RESULTS
We describe calcium waves arising exclusively in non-neuronal retinal support cells during the development of the Drosophila compound eye. To achieve this, we optimized a dry-lens–based imaging platform that enables robust, versatile in vivo calcium imaging. We found that the waves are sparsely initiated in single ommatidia (unit eyes) by activation of the receptor tyrosine kinase Cad96Ca in one of the four lens-forming “cone cells.” This activates phospholipase C–γ (PLC-γ), leading to calcium release from the endoplasmic reticulum via inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs). The calcium signal first propagates vertically to all retinal cells within a single ommatidium (see the figure, panel A), with the exception of photoreceptors, and then laterally to neighboring ommatidia, forming waves that spread across large regions of the retina (see the figure, panels A and B). This propagation occurs through gap junction channels composed of combinations of innexin subunits that differ between different cell types. This cell type–specific “innexin code” determines the order of signal propagation and shapes regional calcium signaling levels.
These wave-induced calcium signals drive myosin II–mediated apical contractions at interommatidial boundaries. The intensity of the calcium signal scales with ommatidial size, with waves occurring more frequently in the antero-ventral region where ommatidia are larger. This size-matched activity thus drives stronger apical contractions in regions with larger boundaries. Through this process, calcium waves progressively remodel the retinal epithelium, correcting early boundary disparities and aligning ommatidia into a uniform array (see the figure, panel C). This developmental remodeling ensures a smooth optical surface and precise lens alignment, potentially accommodating the distinct visual demands of small dorsal ommatidia facing the bright sky and large ground-facing ventral ommatidia optimized for sensitivity.
CONCLUSION
Our findings show that synchronized calcium activity within non-neuronal cells directs the coordinated assembly of sensory tissue architecture. The conserved presence of gap junction–mediated calcium waves in vertebrate glia and epithelia suggests that similar mechanisms integrate cellular patterning with physiological function in many systems.
Retinal calcium waves shape regional calcium signals, coordinating ommatidial remodeling.
(A and B) Waves initiate in a cone cell (CC) and follow a stereotypic pathway, propagating vertically from the CC to the primary pigment cell (1PC), then to interommatidial cells (IOCs) within the same ommatidium, and laterally across neighboring ommatidia. (C) Wave intensity scales with ommatidial size, correcting initial boundary irregularities to produce uniformly packed ommatidia across the retina.
Abstract
Optimal neural processing relies on precise tissue patterning across diverse cell types. Here, we show that spontaneous calcium waves arise among non-neuronal support cells in the developing Drosophila eye to drive retinal morphogenesis. These waves are initiated by Cad96Ca receptor tyrosine kinase signaling, triggering phospholipase C–γ–mediated calcium release from the endoplasmic reticulum. A cell type–specific “innexin code” coordinates wave propagation through a defined gap junction network among non-neuronal retinal cells, excluding photoreceptors. Wave intensity scales with ommatidial size, triggering stronger myosin II–driven apical contraction at interommatidial boundaries in larger ommatidia. This size-dependent mechanism compensates for early boundary irregularities, ensuring uniform ommatidial packing that is critical for precise optical architecture. Our findings reveal how synchronized calcium signaling among non-neuronal cells orchestrates tissue patterning in the developing nervous system.
