Rho guanine nucleotide exchange factor xNET1 implicated in gastrulation movements during Xenopus development

Miyakoshi, Akira; Ueno, Naoto; Kinoshita, Noriyuki

doi:10.1111/j.1432-0436.2004.07201004.x

Cited by 35 publications

(25 citation statements)

References 35 publications

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“…Control of GTPase activity via an interaction with GEFs could provide an explanation for previously observed phenotypes that currently lack mechanistic explanation. Numerous studies have demonstrated the critical role for Rac/Cdc42 during gastrulation and convergent extension of Xenopus (35)(36)(37)(38)(39). Our laboratory previously described a defect in epithelial migration upon knockdown of Bves expression by using morpholino oligonucleotides on developing Xenopus embryos.…”

Section: Modulation Of Rac/cdc42 Activity By Bves Is Consistent With mentioning

confidence: 99%

Bves directly interacts with GEFT, and controls cell shape and movement through regulation of Rac1/Cdc42 activity

Smith

Hager

Francis

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Bves is an integral membrane protein with no determined function and no homology to proteins outside of the Popdc family. It is widely expressed throughout development in myriad organisms. Here, we demonstrate an interaction between Bves and guanine nucleotide exchange factor T (GEFT), a GEF for Rho-family GTPases. This interaction represents the first identification of any protein that has a direct physical interaction with any member of the Popdc family. Bves and GEFT are shown to colocalize in adult skeletal muscle. We also demonstrate that exogenous expression of Bves reduces Rac1 and Cdc42 activity levels while not affecting levels of active RhoA. Consistent with a repression of Rac1 and Cdc42 activity, we show changes in speed of cell locomotion and cell roundness also result from exogenous expression of Bves. Modulation of Rho-family GTPase signaling by Bves would be highly consistent with previously described phenotypes occurring upon disruption of Bves function in a wide variety of model systems. Therefore, we propose Bves as a novel regulator of the Rac1 and Cdc42 signaling cascades.Popdc ͉ cell motility ͉ GEF

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Section: Modulation Of Rac/cdc42 Activity By Bves Is Consistent With mentioning

confidence: 99%

Bves directly interacts with GEFT, and controls cell shape and movement through regulation of Rac1/Cdc42 activity

Smith

Hager

Francis

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…While most work on small G-proteins during gastrulation has focused on the role of noncanonical Wnts in controlling their activity (Habas et al 2003), several other regulators of Rho or Rac are required for proper gastrulation. These include Has2-dependent (Bakkers et al 2004), Fyn/Yes-dependent (Jopling and den Hertog 2005), and G␣12/G␣13-dependent pathways (Lin et al 2005) as well as several guanine nucleotide exchange factors, which can directly activate small G-proteins (Daggett et al 2004;Miyakoshi et al 2004). With several distinct signaling pathways converging on the Rho family of GTPases as well as other intracellular factors involved in morphogenesis, precise integration of these pathways is essential for proper cell behavior during gastrulation.…”

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confidence: 99%

Gravin regulates mesodermal cell behavior changes required for axis elongation during zebrafish gastrulation

Weiser¹,

Pyati²,

Kimelman³

2007

Genes Dev.

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Convergent extension of the mesoderm is the major driving force of vertebrate gastrulation. During this process, mesodermal cells move toward the future dorsal side of the embryo, then radically change behavior as they initiate extension of the body axis. How cells make this transition in behavior is unknown. We have identified the scaffolding protein and tumor suppressor Gravin as a key regulator of this process in zebrafish embryos. We show that Gravin is required for the conversion of mesodermal cells from a highly migratory behavior to the medio-laterally intercalative behavior required for body axis extension. In the absence of Gravin, paraxial mesodermal cells fail to shut down the protrusive activity mediated by the Rho/ROCK/ Myosin II pathway, resulting in embryos with severe extension defects. We propose that Gravin functions as an essential scaffold for regulatory proteins that suppress the migratory behavior of the mesoderm during gastrulation, and suggest that this function also explains how Gravin inhibits invasive behaviors in metastatic cells.[Keywords: AKAP; convergence and extension; gastrulation; Gravin; Rho; zebrafish] Supplemental material is available at http://www.genesdev.org. Vertebrate gastrulation involves a tightly regulated series of cellular rearrangements that coordinate the movements of the three germ layers (endoderm, mesoderm, and ectoderm) to establish the final embryonic body plan (Keller 2002). This process requires a very precise regulation of cell polarity, cell migration, and cell division. One of the major driving forces of vertebrate gastrulation is convergent extension, a mechanism in which mesodermal cells move toward the future dorsal side of the embryo and then intercalate between neighboring cells, resulting in an overall dorsoventral narrowing (convergence) and anteroposterior lengthening (extension) of the embryo (Heisenberg and Tada 2002;Keller 2002; SolnicaKrezel 2006).Mesodermal cells in the zebrafish embryo involved in convergent extension undergo a series of changes starting with a slow dorsal-directed migration, a faster migration as they get closer to the future dorsal side, and then intercalation as they approach the dorsal midline (Concha and Adams 1998; Jessen et al. 2002;Solnica-Krezel 2006). As the mesodermal cells change their behaviors, they undergo a series of morphological changes in cell shape and protrusive activity (Concha and Adams 1998). During early gastrulation, mesodermal cells have an overall rounded phenotype and extend transient lamellipodia and bleb-like protrusions with random orientation (Concha and Adams 1998;. By mid-to late gastrulation, cells become more polarized with lamellipodia that become stabilized and mediolaterally oriented. These cells then migrate in a highly dorsally biased manner. Later in gastrulation, mesodermal cells become tightly packed on the dorsal side of the embryo. These cells, through contact inhibition of migratory behavior, become elongated and firmly attached to their neighboring cells, reduce protrusions,...

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“…The neuroepithelial cell transforming gene net1 encodes a RhoA-specific GEF that regulates cell migration in different embryonic stages of various animal species [38][39][40]. In this study, we found that zebrafish net1 is prominently expressed in the dorsal side of the embryo after MBT.…”

Section: Discussionmentioning

confidence: 57%

“…In Xenopus, Net1 associates with Dishevelled and activates RhoA to regulate gastrulation [38]. In chick gastrulation-stage embryos, reducing Net1 or RhoA expression in epiblast cells prior to the epithelial-to-mesenchymal transition (EMT) leads to ingression and migration defects [39].…”

Section: Introductionmentioning

confidence: 99%

The guanine nucleotide exchange factor Net1 facilitates the specification of dorsal cell fates in zebrafish embryos by promoting maternal β-catenin activation

et al. 2016

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Wnt/β-catenin signaling is essential for the initiation of dorsal-ventral patterning during vertebrate embryogenesis. Maternal β-catenin accumulates in dorsal marginal nuclei during cleavage stages, but its critical target genes essential for dorsalization are silent until mid-blastula transition (MBT). Here, we find that zebrafish net1, a guanine nucleotide exchange factor, is specifically expressed in dorsal marginal blastomeres after MBT, and acts as a zygotic factor to promote the specification of dorsal cell fates. Loss-and gain-of-function experiments show that the GEF activity of Net1 is required for the activation of Wnt/β-catenin signaling in zebrafish embryos and mammalian cells. Net1 dissociates and activates PAK1 dimers, and PAK1 kinase activation causes phosphorylation of S675 of β-catenin after MBT, which ultimately leads to the transcription of downstream target genes. In summary, our results reveal that Net1-regulated β-catenin activation plays a crucial role in the dorsal axis formation during zebrafish development.

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Rho guanine nucleotide exchange factor xNET1 implicated in gastrulation movements during Xenopus development

Cited by 35 publications

References 35 publications

Bves directly interacts with GEFT, and controls cell shape and movement through regulation of Rac1/Cdc42 activity

Bves directly interacts with GEFT, and controls cell shape and movement through regulation of Rac1/Cdc42 activity

Gravin regulates mesodermal cell behavior changes required for axis elongation during zebrafish gastrulation

The guanine nucleotide exchange factor Net1 facilitates the specification of dorsal cell fates in zebrafish embryos by promoting maternal β-catenin activation

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