Regulator of G Protein Signaling 3 Modulates Wnt5b Calcium Dynamics and Somite Patterning

Freisinger, Christina M.; Fisher, Rory A.; Slusarski, Diane C.

doi:10.1371/journal.pgen.1001020

Cited by 20 publications

(17 citation statements)

References 69 publications

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“…During early zebrafish development, Ca 2 þ signalling is primordial during morphogenetic movements 26 . Moreover, C&E movements appear to be partially under the control of the Wnt/ PCP pathway and small GTPases such as RhoaA; thus, these movements could be regulated by calcium signalling 9,27 . We therefore investigated the effect of mcu knockdown on RhoA activation in human cells using a Rhotekin pull-down experiment.…”

Section: Resultsmentioning

confidence: 99%

Bcl-wav and the mitochondrial calcium uniporter drive gastrula morphogenesis in zebrafish

et al. 2013

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Bcl-2 proteins are acknowledged as key regulators of programmed cell death. However, increasing data suggest additional roles, including regulation of the cell cycle, metabolism and cytoskeletal dynamics. Here we report the discovery and characterization of a new Bcl-2-related multidomain apoptosis accelerator, Bcl-wav, found in fish and frogs. Genetic and molecular studies in zebrafish indicate that Bcl-wav and the recently identified mitochondrial calcium uniporter (MCU) contribute to the formation of the notochord axis by controlling blastomere convergence and extension movements during gastrulation. Furthermore, we found that Bcl-wav controls intracellular Ca 2 þ trafficking by acting on the mitochondrial voltage-dependent anion channel, and possibly on MCU, with direct consequences on actin microfilament dynamics and blastomere migration guidance. Thus, from an evolutionary point of view, the original function of Bcl-2 proteins might have been to contribute in controlling the global positioning system of blastomeres during gastrulation, a critical step in metazoan development.

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Section: Resultsmentioning

confidence: 99%

Bcl-wav and the mitochondrial calcium uniporter drive gastrula morphogenesis in zebrafish

et al. 2013

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“…Development 139 (3) and fzd10, and genes encoding components of the Wnt/PCP pathway, such as wnt5b and fzd2, are co-expressed near or within KV (Oishi et al, 2006;Lin and Xu, 2009;Freisinger et al, 2010). Therefore, it is possible that the Wnt/-catenin pathway governs the expression of genes that are essential for cilia formation, whereas the PCP pathway ensures that these cilia-forming components are assembled at a correctly polarized subcellular location, such as the apical surface.…”

Section: Research Articlementioning

confidence: 99%

Wnt/β-catenin signaling directly regulates Foxj1 expression and ciliogenesis in zebrafish Kupffer’s vesicle

2012

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SUMMARYCilia are essential for normal development. The composition and assembly of cilia has been well characterized, but the signaling and transcriptional pathways that govern ciliogenesis remain poorly studied. Here, we report that Wnt/-catenin signaling directly regulates ciliogenic transcription factor foxj1a expression and ciliogenesis in zebrafish Kupffer's vesicle (KV). We show that Wnt signaling acts temporally and KV cell-autonomously to control left-right (LR) axis determination and ciliogenesis. Specifically, reduction of Wnt signaling leads to a disruption of LR patterning, shorter and fewer cilia, a loss of cilia motility and a downregulation of foxj1a expression. However, these phenotypes can be rescued by KV-targeted overexpression of foxj1a. In comparison to the FGF pathway that has been previously implicated in the control of ciliogenesis, our epistatic studies suggest a more downstream function of Wnt signaling in the regulation of foxj1a expression and ciliogenesis in KV. Importantly, enhancer analysis reveals that KV-specific expression of foxj1a requires the presence of putative Lef1/Tcf binding sites, indicating that Wnt signaling activates foxj1a transcription directly. We also find that impaired Wnt signaling leads to kidney cysts and otolith disorganization, which can be attributed to a loss of foxj1 expression and disrupted ciliogenesis in the developing pronephric ducts and otic vesicles. Together, our data reveal a novel role of Wnt/-catenin signaling upstream of ciliogenesis, which might be a general developmental mechanism beyond KV. Moreover, our results also prompt a hypothesis that certain developmental effects of the Wnt/-catenin pathway are due to the activation of Foxj1 and cilia formation. KEY WORDS: Wnt/-catenin signaling, Ciliogenesis, Foxj1, Kupffer's vesicle ZebrafishWnt/-catenin signaling directly regulates Foxj1 expression and ciliogenesis in zebrafish Kupffer's vesicle

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“…In addition, we also focused on the nonhematological phenotype, as it was immediately obvious that RGS18-knockdown embryos also present with a reduced response to acoustic stimuli. Since it was previously shown that RGS proteins have an important role in the regulation of Wnt signaling (15)(16)(17), we also focused on the role of RGS18 in the G-protein-modulated Wnt/calcium pathway.…”

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confidence: 99%

Regulator of G‐protein signaling 18 controls megakaryopoiesis and the cilia‐mediated vertebrate mechanosensory system

et al. 2012

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RGS18 was originally identified as a R4 subfamily member of regulators of G-protein signaling (RGS) with specific expression in hematopoietic progenitors, myeloerythroid cells, and megakaryocytes, though its physiological role in hematopoiesis remained unknown. Here, we show that lentiviral RGS18 overexpression during differentiation of mouse Sca1(+) hematopoietic stem cells induced a 50% increase of megakaryocyte proliferation. RGS18 depletion in zebrafish results in thrombocytopenia, as 66 to 88% of the embryos lack thrombocytes after injection of an ATG or splice-blocking morpholino, respectively. These embryos have no defects in early hematopoiesis, erythropoiesis, or leukocyte number and migration. In addition, all RGS18 depleted embryos have curly tails and an almost absent response to acoustic stimuli. In situ hybridization in zebrafish, Xenopus, and mouse embryos shows RGS18 expression in thrombocytes and/or hematological tissues but also in brain and otic vesicles. RGS18 interferes with development of cilia in hair cells of the inner ear and neuromast cells. On the basis of literature evidence that RGS-R4 members interact with the G-protein-modulated Wnt/calcium pathway, Wnt5b- but not Wnt5a-depleted embryos phenocopy all RGS18 knockdown effects. In summary, our study is the first to show that RGS18 regulates megakaryopoiesis but also reveals its unexpected role in ciliogenesis, at least in lower vertebrates, via interference with Wnt signaling.

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Regulator of G Protein Signaling 3 Modulates Wnt5b Calcium Dynamics and Somite Patterning

Cited by 20 publications

References 69 publications

Bcl-wav and the mitochondrial calcium uniporter drive gastrula morphogenesis in zebrafish

Bcl-wav and the mitochondrial calcium uniporter drive gastrula morphogenesis in zebrafish

Wnt/β-catenin signaling directly regulates Foxj1 expression and ciliogenesis in zebrafish Kupffer’s vesicle

Regulator of G‐protein signaling 18 controls megakaryopoiesis and the cilia‐mediated vertebrate mechanosensory system

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