Live Imaging of Hippo Pathway Components in Drosophila Imaginal Discs

Xu, Jiajie; Su, Ting; Tokamov, Sherzod A; Fehon, Richard G.

doi:10.1007/978-1-4939-8910-2_4

Cited by 5 publications

(3 citation statements)

References 8 publications

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“…Throughout the paper (except in Figure 2F–G’’’ and Figure 2—figure supplement 2A–E ), live tissues were used for imaging. Live imaging of the Drosophila imaginal tissues was performed as previously described ( Xu et al, 2019 ). Briefly, freshly dissected wing or eye imaginal discs from third instar larvae were pipetted into a ~40 μl droplet of Schneider’s Drosophila Medium supplemented with 10% fetal bovine serum and mounted on a glass slide.…”

Section: Methodsmentioning

confidence: 99%

Negative feedback couples Hippo pathway activation with Kibra degradation independent of Yorkie-mediated transcription

Tokamov

Ullyot

et al. 2021

eLife

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The Hippo pathway regulates tissue growth in many animals. Multiple upstream components promote Hippo pathway activity, but the organization of these different inputs, the degree of crosstalk between them, and whether they are regulated in a distinct manner is not well understood. Kibra activates the Hippo pathway by recruiting the core Hippo kinase cassette to the apical cortex. Here we show that the Hippo pathway downregulates Drosophila Kibra levels independently of Yorkie-mediated transcription. We find that Hippo signaling complex formation promotes Kibra degradation via SCFSlimb-mediated ubiquitination, that this effect requires Merlin, Salvador, Hippo, and Warts, and that this mechanism functions independently of other upstream Hippo pathway activators. Moreover, Kibra degradation appears patterned by differences in mechanical tension across the wing. We propose that Kibra degradation mediated by Hippo pathway components and regulated by cytoskeletal tension serves to control Kibra-driven Hippo pathway activation and ensure optimally scaled and patterned tissue growth.

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Section: Methodsmentioning

confidence: 99%

Negative feedback couples Hippo pathway activation with Kibra degradation independent of Yorkie-mediated transcription

Tokamov

Ullyot

et al. 2021

eLife

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“…Throughout the study (except in Figures 2, A–C’ and 4, A–D’ ; Supplemental Figures S1, A–A’ and S5, A–D’), wing imaginal discs were imaged live. Imaging of live tissues was performed as previously described ( Xu et al. , 2019 ).…”

Section: Methodsmentioning

confidence: 99%

Cortical tension promotes Kibra degradation via Par-1

Tokamov,

Buiter,

Ullyot

et al. 2024

MBoC

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The Hippo pathway is an evolutionarily conserved regulator of tissue growth. Multiple Hippo signaling components are regulated via proteolytic degradation. However, how these degradation mechanisms are themselves modulated remains unexplored. Kibra is a key upstream pathway activator that promotes its own ubiquitin-mediated degradation upon assembling a Hippo signaling complex. Here, we demonstrate that Hippo complex-dependent Kibra degradation is modulated by cortical tension. Using classical genetic, osmotic, and pharmacological manipulations of myosin activity and cortical tension, we show that increasing cortical tension leads to Kibra degradation, whereas decreasing cortical tension increases Kibra abundance. Our study also implicates Par-1 in regulating Kib abundance downstream of cortical tension. We demonstrate that Par-1 promotes ubiquitin-mediated Kib degradation in a Hippo complex-dependent manner and is required for tension-induced Kib degradation. Collectively, our results reveal a previously unknown molecular mechanism by which cortical tension affects Hippo signaling and provide novel insights into the role of mechanical forces in growth control. [Media: see text] [Media: see text] [Media: see text]

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“…Live imaging of the Drosophila imaginal tissues was performed as previously described (Xu et al, 2019). Briefly, freshly dissected wing or eye imaginal discs from third instar larvae were pipetted into a ~40µl droplet of Schneider's Drosophila Medium supplemented with 10% Fetal Bovine Serum and mounted on a glass slide.…”

Section: Live Imaging Of Imaginal Tissuesmentioning

confidence: 99%

Yorkie-independent negative feedback couples Hippo pathway activation with Kibra degradation

Tokamov

Ullyot

et al. 2020

Preprint

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AbstractThe Hippo signaling pathway regulates tissue growth in many animals. Multiple upstream components are known to promote Hippo pathway activity, but the organization of these different inputs, the degree of crosstalk between them, and whether they are regulated in a distinct manner is not well understood. Kibra activates the Hippo pathway by recruiting the core Hippo kinase cassette to the apical cortex. Here we show that the Hippo pathway downregulates Kibra levels independently of Yorkie-mediated transcriptional output. We find that the Hippo pathway promotes Kibra degradation via SCFSlimb-mediated ubiquitination, that this effect requires the core kinases Hippo and Warts, and that this mechanism functions independently of other upstream Hippo pathway activators including Crumbs and Expanded. Moreover, Kibra degradation appears patterned across tissue. We propose that Kibra degradation by the Hippo pathway serves as a negative feedback loop to tightly control Kibra-mediated Hippo pathway activation and ensure optimally scaled and patterned tissue growth.

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Live Imaging of Hippo Pathway Components in Drosophila Imaginal Discs

Cited by 5 publications

References 8 publications

Negative feedback couples Hippo pathway activation with Kibra degradation independent of Yorkie-mediated transcription

Negative feedback couples Hippo pathway activation with Kibra degradation independent of Yorkie-mediated transcription

Cortical tension promotes Kibra degradation via Par-1

Yorkie-independent negative feedback couples Hippo pathway activation with Kibra degradation

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