Hippo signalling controls Dronc activity to regulate organ size in Drosophila

Verghese, Shilpi; Bedi, Shimpi; Kango‐Singh, Madhuri

doi:10.1038/cdd.2012.48

Cited by 48 publications

(43 citation statements)

References 40 publications

(71 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2F). These data further validate other studies demonstrating that gain of function of hpo primarily induces cell death (Verghese et al, 2012). However, our data also show that Yki affects eye differentiation; therefore, we tested the expression of core RD genes when Yki is activated.…”

Section: Yki Activation Regulates Eye Developmentsupporting

confidence: 66%

“…2D). This decrease in size and number of photoreceptors may be attributed to the induction of cell death by hyperactivation of the Hippo pathway (Tapon et al, 2002;Udan et al, 2003;Verghese et al, 2012). Therefore, we analyzed gain-of-function 'flp-out' clones of hpo in the eye that were generated during the late second instar stage.…”

Section: Yki Activation Regulates Eye Developmentmentioning

confidence: 99%

“…Hyperactivation of the Hippo pathway (e.g. by overexpression of Hpo or Ex) induces apoptosis, leading to the formation of smaller organs and inactivation of Yki (Harvey et al, 2003;Udan et al, 2003;Wu et al, 2003;Verghese et al, 2012Verghese et al, , 2013; however, its downregulation (e.g. by loss of function of ex, hpo, sav, wts and mats) results in overgrowth and activation of Yki.…”

Section: Introductionmentioning

confidence: 99%

“…Growth regulatory pathways play an important role during organogenesis to regulate patterning, growth and differentiation (Raff, 1996;Baker, 2001;Tumaneng et al, 2012;Verghese et al, 2012Verghese et al, , 2013Pichaud, 2014). These pathways crosstalk with each other, and are re-utilized to generate complexity and diverse cell types in different organisms (Pires-daSilva and Sommer, 2003;Jukam and Desplan, 2011;Jukam et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The Hippo pathway effector Yki downregulates Wg signaling to promote retinal differentiation in the Drosophila eye

et al. 2015

View full text Add to dashboard Cite

The evolutionarily conserved Hippo signaling pathway is known to regulate cell proliferation and maintain tissue homeostasis during development. We found that activation of Yorkie (Yki), the effector of the Hippo signaling pathway, causes separable effects on growth and differentiation of the Drosophila eye. We present evidence supporting a role for Yki in suppressing eye fate by downregulation of the core retinal determination genes. Other upstream regulators of the Hippo pathway mediate this effect of Yki on retinal differentiation. Here, we show that, in the developing eye, Yki can prevent retinal differentiation by blocking morphogenetic furrow (MF) progression and R8 specification. The inhibition of MF progression is due to ectopic induction of Wingless (Wg) signaling and Homothorax (Hth), the negative regulators of eye development. Modulating Wg signaling can modify Yki-mediated suppression of eye fate. Furthermore, ectopic Hth induction due to Yki activation in the eye is dependent on Wg. Last, using Cut (Ct), a marker for the antennal fate, we show that suppression of eye fate by hyperactivation of yki does not change the cell fate (from eye to antenna-specific fate). In summary, we provide the genetic mechanism by which yki plays a role in cell fate specification and differentiation -a novel aspect of Yki function that is emerging from multiple model organisms.

show abstract

Section: Yki Activation Regulates Eye Developmentsupporting

confidence: 66%

Section: Yki Activation Regulates Eye Developmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Hippo pathway effector Yki downregulates Wg signaling to promote retinal differentiation in the Drosophila eye

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Immunofluorescence was performed as described (25) and the images were captured using the Olympus Fluoview 1000 confocal microscope.…”

Section: Methodsmentioning

confidence: 99%

FOXD1–ALDH1A3 Signaling Is a Determinant for the Self-Renewal and Tumorigenicity of Mesenchymal Glioma Stem Cells

et al. 2016

View full text Add to dashboard Cite

Glioma stem-like cells (GSC) with tumor initiating activity orchestrate the cellular hierarchy in glioblastoma (GBM) and engender therapeutic resistance. Recent work has divided GSC into two subtypes with a mesenchymal (MES) GSC population as the more malignant subtype. In this study, we identify the FOXD1-ALDH1A3 signaling axis as a determinant of the MES GSC phenotype. The transcription factor FOXD1 is expressed predominantly in patient-derived cultures enriched with MES, but not with the proneural (PN) GSC subtype. shRNA-mediated attenuation of FOXD1 in MES GSC ablates their clonogenicity in vitro and in vivo. Mechanistically, FOXD1 regulates the transcriptional activity of ALDH1A3, an established functional marker for MES GSC. Indeed, the functional roles of FOXD1 and ALDH1A3 are likely evolutionally conserved, insofar as RNAi-mediated attenuation of their orthologous genes in Drosophila blocks formation of brain tumors engineered in that species. In clinical specimens of high-grade glioma, the levels of expression of both FOXD1 and ALDH1A3 are inversely correlated with patient prognosis. Lastly, a novel small molecule inhibitor of ALDH we developed, termed GA11, displays potent in vivo efficacy when administered systemically in a murine GSC-derived xenograft model of GBM. Collectively, our findings define a FOXD1-ALDH1A3 pathway in controlling the clonogenic and tumorigenic potential of MES GSC in GBM tumors.

show abstract

An E3 ubiquitin ligase, cullin‐4 regulates retinal differentiation in Drosophila eye

Tare

Chimata

Gogia

et al. 2020

Genesis

View full text Add to dashboard Cite

During organogenesis, cell proliferation is followed by the differentiation of specific cell types to form an organ. Any aberration in differentiation can result in developmental defects, which can result in a partial to a near-complete loss of an organ. We employ the Drosophila eye model to understand the genetic and molecular mechanisms involved in the process of differentiation. In a forward genetic screen, we identified, cullin-4 (cul-4), which encodes an E3 ubiquitin ligase, to play an important role in retinal differentiation. During development, cul-4 is known to be involved in protein degradation, regulation of genomic stability, and regulation of cell cycle. Previously, we have reported that cul-4 regulates cell death during eye development by downregulating Wingless (Wg)/Wnt signaling pathway. We found that loss-offunction of cul-4 results in a reduced eye phenotype, which can be due to onset of cell death. However, we found that loss-of-function of cul-4 also affects retinal development by downregulating retinal determination (RD) gene expression. Early markers of retinal differentiation are dysregulated in cul-4 loss of function conditions, indicating that cul-4 is necessary for differentiation. Furthermore, loss-of-function of cul-4 ectopically induces expression of negative regulators of eye development like Wg and Homothorax (Hth). During eye development, Wg is known to block the progression of a synchronous wave of differentiation referred to as Morphogenetic furrow (MF). In cul-4 loss-of-function background, expression of dpp-lacZ, a MF marker, is significantly downregulated. Our data suggest a new role of cul-4 in retinal differentiation. These studies may have significant bearings on our understanding of early eye development.

show abstract

Hippo signalling controls Dronc activity to regulate organ size in Drosophila

Cited by 48 publications

References 40 publications

The Hippo pathway effector Yki downregulates Wg signaling to promote retinal differentiation in the Drosophila eye

The Hippo pathway effector Yki downregulates Wg signaling to promote retinal differentiation in the Drosophila eye

FOXD1–ALDH1A3 Signaling Is a Determinant for the Self-Renewal and Tumorigenicity of Mesenchymal Glioma Stem Cells

An E3 ubiquitin ligase, cullin‐4 regulates retinal differentiation in Drosophila eye

Contact Info

Product

Resources

About