A protease-initiated model of wound detection

O’Connor, James T.; Stevens, Aaron C.; Shannon, Erica K.; Akbar, Fabiha Bushra; LaFever, Kimberly S.; Narayanan, Neil; Hutson, M. Shane; Page-McCaw, Andrea

doi:10.1101/2020.12.08.415554

Cited by 5 publications

(2 citation statements)

References 61 publications

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“…These results are consistent with previous reports of Ca 2+ spikes being observed in discs that have reached their final size, and Ca 2+ waves being observed in smaller developing discs [19]. A recent study found that Ca 2 + signals are initiated in response to wounding by the G-protein coupled receptor Methuselah like 10 (Mthl10) [60]. Mthl10 is activated by Growth-blocking peptides (Gbps) [60].…”

Section: Discussionsupporting

confidence: 92%

“…A recent study found that Ca 2 + signals are initiated in response to wounding by the G-protein coupled receptor Methuselah like 10 (Mthl10) [60]. Mthl10 is activated by Growth-blocking peptides (Gbps) [60]. Whether Mthl10 also is involved in developmental growth requires further investigation, but may be consistent with our findings that intercellular calcium wave activity inhibits organ growth.…”

Section: Discussionsupporting

confidence: 89%

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confidence: 92%

Section: Discussionsupporting

confidence: 89%

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Zones of Cellular Damage Around Pulsed-Laser Wounds

O’Connor

Akbar

Hutson

et al. 2021

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After a tissue is wounded, cells surrounding the wound adopt distinct wound-healing behaviors to repair the tissue. Considerable effort has been spent on understanding the signaling pathways that regulate immune and tissue-resident cells as they respond to wounds, but these signals must ultimately originate from the physical damage inflicted by the wound. Tissue wounds comprise several types of cellular damage, and recent work indicates that different types of cellular damage initiate different types of signaling. Hence to understand wound signaling, it is important to identify and localize the types of wound-induced cellular damage. Laser ablation is widely used by researchers to create reproducible, aseptic wounds in a tissue that can be live-imaged. Because laser wounding involves a combination of photochemical, photothermal and photomechanical mechanisms, each with distinct spatial dependencies, cells around a pulsed-laser wound will experience a gradient of damage. Here we exploit this gradient to create a map of wound-induced cellular damage. Using genetically-encoded fluorescent proteins, we monitor damaged cellular and sub-cellular components of epithelial cells in living Drosophila pupae in the seconds to minutes following wounding. We hypothesized that the regions of damage would be predictably arrayed around wounds of varying sizes, and subsequent analysis found that all damage radii are linearly related o ver a 3-fold range of wound size . Thus, around laser wounds, the distinct regions of damage can be estimated after measuring any one. This report identifies several different types of cellular damage within a wounded epithelial tissue in a living animal. By quantitatively mapping the size and placement of these different types of damage, we set the foundation for tracing wound-induced signaling back to the damage that initiates it.

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From spikes to intercellular waves: tuning intercellular Ca²⁺signaling dynamics modulates organ size control

Soundarrajan

Huizar

Paravitorghabeh

et al. 2019

Preprint

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Calcium (Ca 2+ ) signaling is a fundamental molecular communication mechanism for the propagation of information in eukaryotic cells. Cytosolic calcium ions integrate a broad range of hormonal, mechanical and electrical stimuli within cells to modulate downstream cellular processes involved in organ development. However, how the spatiotemporal dynamics of calcium signaling are controlled at the organ level remains poorly understood. Here, we show that the spatiotemporal extent of calcium signaling within an epithelial system is determined by the class and level of hormonal stimulation and by the subdivision of the cell population into a small fraction of initiator cells surrounded by a larger fraction of standby cells connected through gap junction communication. To do so, we built a geometrically accurate computational model of intercellular Ca 2+ signaling that spontaneously occurs within developing Drosophila wing imaginal discs. The multi-scale computational model predicts the regulation of the main classes of Ca 2+ signaling dynamics observed in vivo: single cell Ca 2+ spikes, intercellular transient bursts, intercellular waves and global fluttering. We show that the tuning of the spatial extent of Ca 2+ dynamics from single cells to global waves emerges naturally as a function of global hormonal stimulation strength. Further, this model provides insight into how emergent properties of intercellular calcium signaling dynamics modulates cell growth within the tissue context. It provides a framework for analyzing second messenger dynamics in multicellular systems. Second messengers | Gap junction communication | Spatiotemporal patterns | Information processing | Hopf bifurcation. C alcium ions (Ca 2+ ) mediate a large number of physi-1 ological and regulatory processes such as proliferation, 51 Significance StatementIntercellular calcium signaling is critical for epithelial morphogenesis and homeostasis. However, how cytosolic calcium concentration dynamics are regulated at the multicellular level are poorly understood. Here, we show using a novel multiscale computational model that the spatial extent of intercellular calcium communication is controlled by two factors: i) the relative strength of global hormonal stimulation, and ii) the presence of a subset of "initiator cells" among a population of "standby cells" that are connected by gap junctions. Localized multicellular calcium signals are associated with maximal organ growth while persistent calcium waves inhibit overall organ growth. This mechanism explains the broad range of spatiotemporal calcium signaling dynamics that occurs during epithelial development.The experimental data is imaged by Dharsan Soundarrajan 2 .these results support a novel model that links tissue-level 52 calcium signaling dynamics to overall organ size regulation, 53 which we term the "IP3 /Ca 2+ shunt" model. This hypothesis 54 views Ca 2+ signaling as a readout of two physiological states: 55 stimulation of calcium signaling can be either growth promot-56 ing or growth inhibiti...

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A protease-initiated model of wound detection

Cited by 5 publications

References 61 publications

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Zones of Cellular Damage Around Pulsed-Laser Wounds

From spikes to intercellular waves: tuning intercellular Ca²⁺signaling dynamics modulates organ size control

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A protease-initiated model of wound detection

Cited by 5 publications

References 61 publications

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Zones of Cellular Damage Around Pulsed-Laser Wounds

From spikes to intercellular waves: tuning intercellular Ca2+signaling dynamics modulates organ size control

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From spikes to intercellular waves: tuning intercellular Ca²⁺signaling dynamics modulates organ size control