Coordination of Rho Family GTPase Activities to Orchestrate Cytoskeleton Responses during Cell Wound Repair

Abreu-Blanco, María Teresa; Verboon, Jeffrey M.; Parkhurst, Susan M.

doi:10.1016/j.cub.2013.11.048

Cited by 140 publications

(196 citation statements)

References 40 publications

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“…4). Inhibition of Rho kinase has previously been shown to abrogate purse string formation and thereby wound closure in fly and fish embryos (Abreu-Blanco et al, 2014;Gault et al, 2014). However, our analyses point to the absence of purse-string mechanisms during most closure phases of large cutaneous wounds in adult zebrafish, suggesting that other Rock-dependent processes must be affected.…”

Section: Transgenic Inhibition Of Fgf Signalling Does Not Compromise mentioning

confidence: 50%

Re-epithelialization of cutaneous wounds in adult zebrafish combines mechanisms of wound closure in embryonic and adult mammals

Richardson¹,

Metzger²,

Knyphausen³

et al. 2016

Journal of Cell Science

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Re-epithelialization of cutaneous wounds in adult mammals takes days to complete and relies on numerous signalling cues and multiple overlapping cellular processes that take place both within the epidermis and in other participating tissues. Re-epithelialization of partial-or fullthickness skin wounds of adult zebrafish, however, is extremely rapid and largely independent of the other processes of wound healing. Live imaging after treatment with transgene-encoded or chemical inhibitors reveals that re-epithelializing keratinocytes repopulate wounds by TGF-β-and integrin-dependent lamellipodial crawling at the leading edges of the epidermal tongue. In addition, re-epithelialization requires long-range epithelial rearrangements, involving radial intercalations, flattening and directed elongation of cells -processes that are dependent on Rho kinase, JNK and, to some extent, planar cell polarity within the epidermis. These rearrangements lead to a massive recruitment of keratinocytes from the adjacent epidermis and make reepithelialization independent of keratinocyte proliferation and the mitogenic effect of FGF signalling, which are only required after wound closure, allowing the epidermis outside the wound to re-establish its normal thickness. Together, these results demonstrate that the adult zebrafish is a valuable in vivo model for studying and visualizing the processes involved in cutaneous wound closure, facilitating the dissection of direct from indirect and motogenic from mitogenic effects of genes and molecules affecting wound re-epithelialization.

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Section: Transgenic Inhibition Of Fgf Signalling Does Not Compromise mentioning

confidence: 50%

Re-epithelialization of cutaneous wounds in adult zebrafish combines mechanisms of wound closure in embryonic and adult mammals

Richardson¹,

Metzger²,

Knyphausen³

et al. 2016

Journal of Cell Science

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show abstract

“…The results could improve our understandings for sensing the alterations in gravitational levels. In additiona, the cell shape-dependent control of the cytoskeleton is maintained by the cooperation of RhoA, Rac and Cdc42 proteins [41]. The redistribution of Rho GTPase activities and remodeling of cytoskeleton networks across the cell body should play crucial functions, and a combinational effect from the actions of RhoA with other GTPases is necessary for the cell morphological changes, such as capillary formation during simulated microgravity.…”

Section: Discussionmentioning

confidence: 99%

Simulated Microgravity Promotes Angiogenesis through RhoA-Dependent Rearrangement of the Actin Cytoskeleton

Shi¹,

Wang²,

Hu³

et al. 2017

Cell Physiol Biochem

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Background/aims: Microgravity leads to hydrodynamic alterations in the cardiovascular system and is associated with increased angiogenesis, an important aspect of endothelial cell behavior to initiate new vessel growth. Given the critical role of Rho GTPase-dependent cytoskeleton rearrangement in cell migration, small GTPase RhoA might play a potential role in microgravity-induced angiogenesis. Methods: We examined the organization of actin filaments by FITC-conjugated phalloidin staining, as well as the expression and activity of RhoA by quantitative PCR and Western blot, in human umbilical vein endothelial cells (HUVECs) under normal gravity and simulated microgravity. Effect of simulated microgravity on the wound closure and tube formation in HUVECs, and their dependence on RhoA, were also analyzed by cell migration and tube formation assays. Results: We show that in HUVECs actin filaments are disorganized and RhoA activity is reduced by simulated microgravity. Blocking RhoA activity either by C3 transferase Rho inhibitor or siRNA knockdown mimicked the effect of simulated microgravity on inducing actin filament disassembly, followed by enhanced wound closure and tube formation in HUVECs, which closely resembled effects seen on microgravity-treated cells. In contrast, overexpressing RhoA in microgravity-treated HUVECs restored the actin filaments, and decreased wound closure and tube formation abilities. Conclusion: These results suggest that RhoA inactivation is involved in the actin rearrangement-associated angiogenic responses in HUVECs during simulated microgravity.

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“…Two biosensors were used to determine Rho1 activity: Capu-RBD-GFP and Dia-RBD-GFP (Abreu-Blanco et al, 2014). Capu-RBD-GFP fluorescence was strong at the posterior of the germarium.…”

Section: Cdc42mentioning

confidence: 99%

Escort cells generate a dynamic compartment for germline stem cell differentiation via combined Stat and Erk signalling

Banisch¹,

Maimon²,

Dadosh³

et al. 2017

Journal of Cell Science

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Two different compartments support germline stem cell (GSC) selfrenewal and their timely differentiation: the classical niche provides maintenance cues, while a differentiation compartment, formed by somatic escort cells (ECs), is required for proper GSC differentiation. ECs extend long protrusions that invade between tightly packed germ cells, and alternate between encapsulating and releasing them. How ECs achieve this dynamic balance has not been resolved. By combining live imaging and genetic analyses in Drosophila, we have characterised EC shapes and their dynamic changes. We show that germ cell encapsulation by ECs is a communal phenomenon, whereby EC-EC contacts stabilise an extensive meshwork of protrusions. We further show that Signal Transducer and Activator of Transcription (Stat) and Epidermal Growth Factor Receptor (Egfr) signalling sustain EC protrusiveness and flexibility by combinatorially affecting the activity of different RhoGTPases. Our results reveal how a complex signalling network can determine the shape of a cell and its dynamic behaviour. It also explains how the differentiation compartment can establish extensive contacts with germ cells, while allowing a continual posterior movement of differentiating GSC daughters.

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Coordination of Rho Family GTPase Activities to Orchestrate Cytoskeleton Responses during Cell Wound Repair

Cited by 140 publications

References 40 publications

Re-epithelialization of cutaneous wounds in adult zebrafish combines mechanisms of wound closure in embryonic and adult mammals

Re-epithelialization of cutaneous wounds in adult zebrafish combines mechanisms of wound closure in embryonic and adult mammals

Simulated Microgravity Promotes Angiogenesis through RhoA-Dependent Rearrangement of the Actin Cytoskeleton

Escort cells generate a dynamic compartment for germline stem cell differentiation via combined Stat and Erk signalling

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