Rho1 has multiple functions in Drosophila wing planar polarity

Yan, Jie; Lu, Qiuheng; Fang, Xiaolan; Adler, Paul N.

doi:10.1016/j.ydbio.2009.06.027

Cited by 37 publications

(50 citation statements)

References 72 publications

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“…Mwh-GBD-FH3 shows in vivo activity Previously, we generated transgenic flies in which we could induce the expression of N-or C-terminal partial Mwh proteins (Yan et al, 2009). No gain-of-function phenotype was seen when either of these was expressed.…”

Section: Hair Development In Mwh Mutantsmentioning

confidence: 99%

“…Disruption of either by drug treatment leads to cells forming multiple hairs (Guild et al, 2005;Shimada et al, 2006;Turner and Adler, 1998). In addition, loss-of-function mutations in Drosophila actin cytoskeleton regulators, such as the small GTPases Rho1 and Cdc42, the Rho effector Rho kinase (Rok) and the myosins crinkled (myosin VIIa) and zipper (myosin II), result in multiple wing hair and hair morphology phenotypes (Eaton et al, 1996;Franke et al, 2010;Kiehart et al, 2004;Winter et al, 2001;Yan et al, 2009). We further studied the role of the actin cytoskeleton in hair outgrowth using in vivo imaging and observed that, initially, multiple bundles of F-actin were visible near the distal vertex.…”

Section: Introductionmentioning

confidence: 99%

“…This autoinhibition is relieved by the binding of Rho-GTP to the GBD. It seems likely that the GBD-FH3 domain of Mwh mediates an interaction with Rho-GTP analogous to the interaction between Rho1 and Dia (Yan et al, 2009). Mwh and Rho1 co-immunoprecipitate and Rho1 activity is required for the accumulation of Mwh in wing cells.…”

Section: Introductionmentioning

confidence: 99%

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TheDrosophilaplanar polarity genemultiple wing hairsdirectly regulates the actin cytoskeleton

Schafer

Adler

2015

Development

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The evolutionarily conserved frizzled/starry night (fz/stan) pathway regulates planar cell polarity (PCP) in vertebrates and invertebrates. This pathway has been extensively studied in the Drosophila wing, where it is manifested by an array of distally pointing cuticular hairs. Using in vivo imaging we found that, early in hair growth, cells have multiple actin bundles and hairs that subsequently fuse into a single growing hair. The downstream PCP gene multiple wing hairs (mwh) plays a key role in this process and acts to antagonize the actin cytoskeleton. In mwh mutants hair initiation is not limited to a small region at the distal edge of pupal wing cells as in wild type, resulting in multiple hairs with aberrant polarity. Extra actin bundles/hairs are formed and do not completely fuse, in contrast to wild type. As development proceeded additional hairs continued to form, further increasing hair number. We identified a fragment of Mwh with in vivo rescue activity and that bound and bundled F-actin filaments and inhibited actin polymerization in in vitro actin assays. The loss of these activities can explain the mwh mutant phenotype. Our data suggest a model whereby, prior to hair initiation, proximally localized Mwh inhibits actin polymerization resulting in polarized activation of the cytoskeleton and hair formation on the distal side of wing cells. During hair growth Mwh is found in growing hairs, where we suggest it functions to promote the fusion of actin bundles and inhibit the formation of additional actin bundles that could lead to extra hairs.

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Section: Hair Development In Mwh Mutantsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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TheDrosophilaplanar polarity genemultiple wing hairsdirectly regulates the actin cytoskeleton

Schafer

Adler

2015

Development

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“…Three Rac genes in Drosophila have overlapping functions and it is likely that the Rac1 dominant-negative allele interferes with the function of all Rac genes (Hakeda-Suzuki et al 2002). To reduce Rho1 function, we used a RNAi transgene (Rho1 RNAi ), which has been shown to effectively knockdown Rho1 protein levels and function (Massarwa et al 2009;Yan et al 2009). While expression of Rac1 DN or Rho1 RNAi showed no discernable effects alone (data not shown) or on the ey.Ras ACT phenotype (see Figure S5), Rac1 DN suppressed the cooperation with Rac1 and Ras ACT , and Rho1 RNAi suppressed Rho1 GS12503 and Rho1 ACT cooperation with Ras ACT , as expected (Table 2; see Figure S6).…”

Section: Uas-pbl-gfp#8mentioning

confidence: 99%

Identification of Novel Ras-Cooperating Oncogenes in Drosophila melanogaster: A RhoGEF/Rho-Family/JNK Pathway Is a Central Driver of Tumorigenesis

et al. 2011

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We have shown previously that mutations in the apico-basal cell polarity regulators cooperate with oncogenic Ras (Ras ACT ) to promote tumorigenesis in Drosophila melanogaster and mammalian cells. To identify novel genes that cooperate with Ras ACT in tumorigenesis, we carried out a genome-wide screen for genes that when overexpressed throughout the developing Drosophila eye enhance Ras ACT -driven hyperplasia. Ras ACT -cooperating genes identified were Rac1 Rho1, RhoGEF2, pbl, rib, and east, which encode cell morphology regulators. In a clonal setting, which reveals genes conferring a competitive advantage over wildtype cells, only Rac1, an activated allele of Rho1 (Rho1 ACT ), RhoGEF2, and pbl cooperated with Ras ACT , resulting in reduced differentiation and large invasive tumors. Expression of RhoGEF2 or Rac1 with Ras ACT upregulated Jun kinase ( JNK) activity, and JNK upregulation was essential for cooperation. However, in the whole-tissue system, upregulation of JNK alone was not sufficient for cooperation with Ras ACT , while in the clonal setting, JNK upregulation was sufficient for Ras ACT -mediated tumorigenesis. JNK upregulation was also sufficient to confer invasive growth of Ras V12 -expressing mammalian MCF10A breast epithelial cells. Consistent with this, HER2 1 human breast cancers (where human epidermal growth factor 2 is overexpressed and Ras signaling upregulated) show a significant correlation with a signature representing JNK pathway activation. Moreover, our genetic analysis in Drosophila revealed that Rho1 and Rac are important for the cooperation of RhoGEF2 or Pbl overexpression and of mutants in polarity regulators, Dlg and aPKC, with Ras ACT in the whole-tissue context. Collectively our analysis reveals the importance of the RhoGEF/ Rho-family/JNK pathway in cooperative tumorigenesis with Ras ACT .

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“…Hence, we consider myosin-interacting proteins as candidates for interacting with Mwh. As noted previously (Yan et al 2009) the C-terminal half of Mwh is sufficient and necessary for it to accumulate in hairs. This part of the protein is not conserved outside of insects and it does not contain any recognizable domains so the molecular biology of Mwh has not provided hints as to what causes it to accumulate in growing hairs.…”

Section: Discussionmentioning

confidence: 52%

The Drosophila Planar Polarity Proteins Inturned and Multiple Wing Hairs Interact Physically and Function Together

Yan²,

Adler

2010

Genetics

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The conserved frizzled ( fz) pathway regulates planar cell polarity in both vertebrate and invertebrate animals. This pathway has been most intensively studied in the wing of Drosophila, where the proteins encoded by pathway genes all accumulate asymmetrically. Upstream members of the pathway accumulate on the proximal, distal, or both cell edges in the vicinity of the adherens junction. More downstream components including Inturned and Multiple Wing Hairs accumulate on the proximal side of wing cells prior to hair initiation. The Mwh protein differs from other members of the pathway in also accumulating in growing hairs. Here we show that the two Mwh accumulation patterns are under different genetic control with the early proximal accumulation being regulated by the fz pathway and the latter hair accumulation being largely independent of the pathway. We also establish recruitment by proximally localized Inturned to be a putative mechanism for the localization of Mwh to the proximal side of wing cells. Genetically inturned (in) acts upstream of mwh (mwh) and is required for the proximal localization of Mwh. We show that Mwh can bind to and co-immunoprecipitate with Inturned. We also show that these two proteins can function in close juxtaposition in vivo. An InTMwh fusion protein provided complete rescue activity for both in and mwh mutations. The fusion protein localized to the proximal side of wing cells prior to hair formation and in growing hairs as expected if protein localization is a key for the function of these proteins.

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Rho1 has multiple functions in Drosophila wing planar polarity

Cited by 37 publications

References 72 publications

TheDrosophilaplanar polarity genemultiple wing hairsdirectly regulates the actin cytoskeleton

TheDrosophilaplanar polarity genemultiple wing hairsdirectly regulates the actin cytoskeleton

Identification of Novel Ras-Cooperating Oncogenes in Drosophila melanogaster: A RhoGEF/Rho-Family/JNK Pathway Is a Central Driver of Tumorigenesis

The Drosophila Planar Polarity Proteins Inturned and Multiple Wing Hairs Interact Physically and Function Together

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