Nuclear signaling by Rac and Rho GTPases is required in the establishment of epithelial planar polarity in the Drosophila eye

Fanto, Manolis; Weber, Ursula; Strutt, David; Mlodzik, Marek

doi:10.1016/s0960-9822(00)00645-x

Cited by 176 publications

(177 citation statements)

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“…XRhoA Activates JNK in the Wnt/PCP Pathway During Xenopus CE Movements JNK is required for tissue polarity in flies and CE movements in frogs in the Wnt/PCP pathway (Strutt et al, 1997;Boutros et al, 1998;Paricio et al, 1999;Fanto et al, 2000;Weber et al, 2000;Yamanaka et al, 2002). Whereas Dsh regulates JNK activation through its DEP domain (Boutros et al, 1998;Li et al, 1999;Moriguchi et al, 1999;Habas et al, 2003), the involvement of Rho GTPases in JNK activation by Dsh remains unclear in mammalian cells (Li et al, 1999;Moriguchi et al, 1999;Habas et al, 2003).…”

Section: Resultsmentioning

confidence: 99%

“…To determine whether RhoA, which genetically interacts with JNK in the PCP pathway in Drosophila (Strutt et al, 1997;Boutros et al, 1998;Fanto et al, 2000;Weber et al, 2000), modulates JNK activation by Dsh during vertebrate CE movements, a kinase assay was performed by using Keller explants. Overexpression of Xdsh increased activity of JNK, and this activation was reduced by coexpression of DN XRhoA (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, it has been known that the Wnt/PCP pathway is an important signal cascade for JNK activation (Veeman et al, 2003b). For example, RhoA and Rac1, but not Cdc42, genetically interact with JNK in PCP pathway in Drosophila (Strutt et al, 1997;Boutros et al, 1998;Fanto et al, 2000;. In mammalian cell system, Rho GTPases also play a critical role in JNK activation by Dsh in Wnt/PCP pathway.…”

Section: Rhoa Is Required For the Activation Of Jnk By Wnt/ Pcp Pathwmentioning

confidence: 99%

“…JNK is required for tissue polarity in flies and for CE movements in frogs (Boutros et al, 1998;Strutt et al, 1997;Paricio et al, 1999;Fanto et al, 2000;Weber et al, 2000;Yamanaka et al, 2002) and is regulated by several core PCP genes (Veeman et al, 2003b). In particular, Rho GTPases, including RhoA, Rac1, and Cdc42, play essential roles in JNK regulation.…”

Section: Introductionmentioning

confidence: 99%

“…In particular, Rho GTPases, including RhoA, Rac1, and Cdc42, play essential roles in JNK regulation. In Drosophila, RhoA and Rac1 but not Cdc42 genetically interact with JNK in PCP pathway (Strutt et al, 1997;Boutros et al, 1998;Fanto et al, 2000;Weber et al, 2000). In HEK293T cell, only Rac1 mediates JNK activation by Dsh (Habas et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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JNK and ROKα function in the noncanonical Wnt/RhoA signaling pathway to regulate Xenopus convergent extension movements

Kim

Han

2005

Developmental Dynamics

104

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The Wnt/planar cell polarity (PCP) pathway plays a critical role in wing, eye, and sensory bristle development of Drosophila and in convergent extension (CE) movements during vertebrate gastrulation. In Drosophila, Jun N-terminal kinase (JNK) and Rho-associated kinase (ROK) participate in RhoA-mediated PCP pathway during eye and wing development. In mammalian cells, Rac1 and Cdc42 but not RhoA are required for JNK activation by Wnt/PCP signals. However, there has been no evidence that Rho GTPases regulate JNK activation in Wnt/PCP pathway during Xenopus CE movements. Here, we report that Xenopus RhoA (XRhoA), but not Xenopus Cdc42 (XCdc42), is essential for JNK activation downstream of the Wnt/PCP pathway during Xenopus CE movements, and the phenotypic effect of loss of XRhoA function was rescued by Xenopus JNK1 (XeJNK1). In addition, XRhoA rescues the inhibition of CE movements by the DEP domain deletion mutant of Xenopus Dsh (Xdsh-⌬DEP), which has dominant negative (DN) effects on JNK activation, and the PDZ domain deletion mutant of Xdsh (Xdsh-⌬PDZ). Moreover, we demonstrate that Xenopus Rho-associated kinase ␣ (xROK␣), which is expressed mainly in mesoderm and ectoderm that undergo extensive cell rearrangements, regulates CE movements without affecting gene expression, and injection of xROK␣ rescued the inhibition of CE movements caused by DN XRhoA. Finally, we show that ROK␣ and JNK synergistically rescued embryos overexpressing DN XRhoA, which exhibit gastrulation defects, although ROK␣ is not required for JNK activation. Together, these data suggest that JNK and ROK␣ function in the noncanonical Wnt/RhoA pathway to regulate Xenopus CE movements. Developmental Dynamics 232: 958 -968, 2005.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Rhoa Is Required For the Activation Of Jnk By Wnt/ Pcp Pathwmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

JNK and ROKα function in the noncanonical Wnt/RhoA signaling pathway to regulate Xenopus convergent extension movements

Kim

Han

2005

Developmental Dynamics

104

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Planar cell polarity genes and neural tube closure

Ueno

Greene

2003

Birth Defects Research Pt C

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Closure of the neural tube is essential for normal development of the brain and spinal cord. Failure of closure results in neural tube defects (NTDs), common and clinically severe congenital malformations whose molecular mechanisms remain poorly understood. On the other hand, it is increasingly well established that common molecular mechanisms are employed to regulate morphogenesis of multicellular organisms. For example, signaling triggered by polypeptide growth factors is highly conserved among species and utilized in multiple developmental processes. Recent studies have revealed that the Drosophila planar cell polarity (PCP) pathway, which directs position and direction of wing hairs on the surface of the fly wing, is well conserved, and orthologs of several genes encoding components of the pathway are also found in vertebrates. Interestingly, in vertebrates, this signaling pathway appears to be co-opted to regulate "convergent extension" cell movements during gastrulation. Disruption of vertebrate PCP genes in Xenopus laevis or zebrafish causes severe gastrulation defects or the shortening of the trunk, as well as mediolateral expansion of somites. In Xenopus, in which the neural tube closes by elevation and fusion of neural folds, inhibition of convergent extension can also prevent neural tube closure causing a "spina bifida-like" appearance. Furthermore, several of the genes involved in the PCP pathway have recently been shown to be required for neural tube closure in the mouse, since mutation of these genes causes NTDs. Therefore, understanding the mechanisms underlying the establishment of cell polarity in Drosophila may provide important clues to the molecular basis of NTDs.

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Dissecting the PCP pathway: One or more pathways?

2011

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Planar cell polarity (PCP), the alignment of cells within 2D tissue planes, involves a set of core molecular regulators highly conserved between animals and cell types. These include the transmembrane proteins Frizzled (Fz) and VanGogh and the cytoplasmic regulators Dishevelled (Dsh) and Prickle. It is widely accepted that this core forms part of a 'PCP pathway' for signal transduction, which can affect cell morphology through activation of an evolutionary ancient regulatory module involving Rho family GTPases and Myosin II, and/or the JNK kinase cascade. We have re-examined the evidence for interactions between the proposed PCP pathway components, and question the placing of the cell morphology regulators in the same pathway as the PCP core. While Fz and Dsh are clearly involved in both PCP and Rho-based cell morphology regulation, available evidence cannot currently discriminate whether these processes are linked mechanistically by a shared Fz/Dsh population, or pass by two distinct pathways.

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Nuclear signaling by Rac and Rho GTPases is required in the establishment of epithelial planar polarity in the Drosophila eye

Abstract: Rac is specifically required downstream of Dsh in the Fz pathway. It functions upstream or in parallel to RhoA and both signal to the nucleus, through distinct effectors, to establish planar polarity in the Drosophila eye.

Cited by 176 publications

References 44 publications

JNK and ROKα function in the noncanonical Wnt/RhoA signaling pathway to regulate Xenopus convergent extension movements

JNK and ROKα function in the noncanonical Wnt/RhoA signaling pathway to regulate Xenopus convergent extension movements

Planar cell polarity genes and neural tube closure

Dissecting the PCP pathway: One or more pathways?

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