Year: 2025
Type: preprint
Abstract: Robust growth control is an essential requirement for the survival of living organisms, while its dysregulation results in diseases such as cancer. However, a significant knowledge gap exists in understanding how precise organ growth control is achieved. The growing arsenal of optogenetic toolkits allows precise, noninvasive control of cellular signaling in vivo, enabling research into how bioelectrical and chemical cues regulate organ growth. Here, we used the red-light-activated channelrhodopsin, CsChrimson, to stimulate intracellular calcium signaling dynamics in the wing epithelium of Drosophila melanogaster , an established model system for investigating organ size control. By varying light intensity and activation dynamics systematically, we identified a biphasic regulation of final organ size. Illumination of CsChrimson depolarizes cells and stimulates spikes of cytosolic calcium concentrations, a phenomenon explained by a computational model that incorporates the inclusion of both gap junction closure and voltage-gated calcium channel activation. This calcium regulation tunes downstream effectors involved in growth regulation and apoptosis. In particular, we found that prolonged bright red light exposure (100 lux/12 hours) increased cell death in wing imaginal discs and caused severe morphological abnormalities in adult wings, with phenotypic severity dependent on stimulation parameters defined by illumination intensity and period of activation. Strikingly, an optimum level of dim, pulsatile light (5 lux, 1 minute on/off pulse train) resulted in overgrown organs and significantly upregulated cell proliferation. We also co-expressed an oncogene, Ras V12 , with CsChrimson and showed that experimental optical simulation parameters can be exploited to control the morphology of tumorous tissues and initiate targeted remission of tumorous growth. Our findings and approach provide a powerful framework to dissect the role of dynamic physiological signaling events in organogenesis and offer translational insights into new therapeutic strategies with applications in cancer and regenerative medicine.
Authors: Mayesha Sahir Mim, Stephen Cini, Caitlin Frank, Zian Wang, Alexander Dowling, Jeremiah J. Zartman
Institution: University of Notre Dame
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Awards: Regulation and function of multicellular calcium signaling in epithelial growth and regeneration, CAREER: Uncertainty Quantification and Optimization with Hybrid Models for Molecular-to-Systems Engineering, G4128767324, BII: Emergent Mechanisms in Biology of Robustness, Integration & Organization (EMBRIO), G8819547208, Regulation and function of multicellular calcium signaling in organ growth and regeneration
OpenAlex ID: W4410599430