XenopusDab2 is required for embryonic angiogenesis

Cheong, Seong-Moon; Choi, Sun‐Cheol; Han, Jin‐Kwan

doi:10.1186/1471-213x-6-63

Cited by 17 publications

(8 citation statements)

References 64 publications

(61 reference statements)

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“…Xenopus laevis eggs were fertilized in vitro (Sive et al 2007 ) and embryos were staged as described (Keller 1991 ). The splicing morpholinos (Genetools) against Xenopus Dab2 ( XDab2 ) were constructed as described previously (Cheong et al 2006 ). Microinjection, whole-mount in situ hybridization, and vibratome sectioning were performed as described in our previous studies (Kam et al 2010 ; Wang et al 2010 ).…”

Section: Methodsmentioning

confidence: 99%

“…Xenopus laevis embryos were hybridized with probes for XDab2 (Cheong et al 2006 ), XPax3 (Zhao et al 2008 ), XMyos (Zhao et al 2007 ), XMyoD (Fisher et al 2002 ), Xac100 (Hemmati-Brivanlou et al 1990 ), and XMyf-5 (Dosch et al 1997 ). XDab2L and XMef2c probes were prepared by subcloning their targeting sequences into the pCS2+ and pBluescript II KS (+/−) vectors, respectively, and plasmids were linearized with HindIII and XhoI accordingly for preparing probe templates.…”

Section: Methodsmentioning

confidence: 99%

“…In our previous study on the expression of Dab2 in the developing central nervous system (Cheung et al 2008 ), strong immunoreactivities were localized to somites and skeletal muscles of mouse embryos. Another study also showed that XDab2 was expressed in somites of Xenopus embryos (Cheong et al 2006 ). Somites are segmental derivatives of the paraxial mesoderm in vertebrate embryos and are one of the embryonic origins of skeletal muscles and satellite cells (Christ and Ordahl 1995 ; Gros et al 2005 ; Schienda et al 2006 ).…”

Section: Introductionmentioning

confidence: 94%

“…Dab2 is expressed in different carcinomas and characterized as a tumor suppressor (Mok et al 1994 ; Schwahn and Medina 1998 ; Tseng et al 1998 ; Huang et al 2001 ). It has also been found in a multitude of tissues and cell types including primitive endodermal cells (Yang et al 2002 ), mesoderm-derived cells such as human K562 cells (Tseng et al 2003 ), endothelial cells (Cheong et al 2006 ), zona glomerulosa of the adrenal cortex (Romero et al 2007 ), bone marrow-derived macrophages and lymphocytes (Rosenbauer et al 2002 ; Jain et al 2009 ), and embryonic stem cells (Huang et al 2010 ). The functions of Dab2 in these tissues and cells have been linked to the regulation of endodermal cell organization, cell adhesion, cell spreading and differentiation, blood vessel formation, aldosterone secretion, and mesoderm differentiation.…”

Section: Introductionmentioning

confidence: 99%

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Disabled-2: a positive regulator of the early differentiation of myoblasts

et al. 2020

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Dab2 is an adaptor protein and a tumor suppressor. Our previous study has found that Dab2 was expressed in early differentiating skeletal muscles in mouse embryos. In this study, we determined the role of Dab2 in the skeletal muscle differentiation using C2C12 myoblasts in vitro and Xenopus laevis embryos in vivo. The expression of Dab2 was increased in C2C12 myoblasts during the formation of myotubes in vitro. Knockdown of Dab2 expression in C2C12 myoblasts resulted in a reduction of myotube formation, whereas the myotube formation was enhanced upon overexpression of Dab2. Re-expression of Dab2 in C2C12 myoblasts with downregulated expression of Dab2 restored their capacity to form myotubes. Microarray profiling and subsequent network analyses on the 155 differentially expressed genes after Dab2 knockdown showed that Mef2c was an important myogenic transcription factor regulated by Dab2 through the p38 MAPK pathway. It was also involved in other pathways that are associated with muscular development and functions. In Xenopus embryos developed in vivo, XDab2 was expressed in the myotome of somites where various myogenic markers were also expressed. Knockdown of XDab2 expression with antisense morpholinos downregulated the expression of myogenic markers in somites. In conclusion, this study is the first to provide solid evidence to show that Dab2 is a positive regulator of the early myoblast differentiation.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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Disabled-2: a positive regulator of the early differentiation of myoblasts

et al. 2020

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“…RT-PCR analysis was performed as described previously (Cheong et al, 2006). Primers for RT-PCR analysis were as follows: March2 forward, 5′-ATGGCTTAAGGACCCAGGAC-3′; March2 reverse, 5′-AGTGGTAGC-GGAATGACACC-3′; Dsh forward, 5′-ATGGCGGAGACTAAAGTGA-TTTA-3′; Dsh reverse, 5′-TTCAGGTCTGACCTCTGTAG-3′; Dpr1 forward, 5′-AGAGCATCTGGAGACAGAC-3′; Dpr1 reverse, 5′-TGTA-GTCCAGCCATTCAAGA-3′.…”

Section: Semi-quantitative Rt-pcrmentioning

confidence: 99%

Head formation requires Dishevelled degradation that is mediated by March2 in concert with Dapper1

et al. 2018

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Dishevelled (Dvl/Dsh) is a key scaffold protein that propagates Wnt signaling essential for embryogenesis and homeostasis. However, whether the antagonism of Wnt signaling that is necessary for vertebrate head formation can be achieved through regulation of Dsh protein stability is unclear. Here, we show that membrane-associated RING-CH2 (March2), a RING-type E3 ubiquitin ligase, antagonizes Wnt signaling by regulating the turnover of Dsh protein via ubiquitin-mediated lysosomal degradation in the prospective head region of We further found that March2 acquires regional and functional specificities for head formation from the Dsh-interacting protein Dapper1 (Dpr1). Dpr1 stabilizes the interaction between March2 and Dsh in order to mediate ubiquitylation and the subsequent degradation of Dsh protein only in the dorso-animal region of embryo. These results suggest that March2 restricts cytosolic pools of Dsh protein and reduces the need for Wnt signaling in precise vertebrate head development.

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Phosphorylation of Dab2 is involved in inhibited VEGF‐VEGFR‐2 signaling induced by downregulation of syndecan‐1 in glomerular endothelial cell

Zhou

Wang

2020

Cell Biology International

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Disabled‐2 (Dab2) and PAR‐3 (partitioning defective 3) are reported to play critical roles in maintaining retinal microvascular endothelial cells biology by regulating VEGF‐VEGFR‐2 signaling. The role of Dab2 and PAR‐3 in glomerular endothelial cell (GEnC) is unclear. In this study, we found that, no matter whether with vascular endothelial growth factor (VEGF) treatment or not, decreased expression of Dab2 could lead to cell apoptosis by preventing activation of VEGF‐VEGFR‐2 signaling in GEnC, accompanied by reduced membrane VEGFR‐2 expression. And silencing of PAR‐3 gene expression caused increased apoptosis of GEnC by inhibiting activation of VEGF‐VEGFR‐2 signaling and membrane VEGFR‐2 expression. In our previous research, we found that the silencing of syndecan‐1 gene expression inhibited VEGF‐VEGFR‐2 signaling by modulating internalization of VEGFR‐2. And our further research demonstrated that downregulation of syndecan‐1 lead to no significant change in the expression of Dab2 and PAR‐3 both at messenger RNA and protein levels in GEnC, while phosphorylation of Dab2 was significantly increased in GEnC transfected with Dab2 small interfering RNA (siRNA) compared with control siRNA. Atypical protein kinase C (aPKC) could induce phosphorylation of Dab2, thus negatively regulating VEGF‐VEGFR‐2 signaling. And we found that decreased expression of syndecan‐1 lead to activation of aPKC, and aPKC inhibitor treatment could block phosphorylation of Dab2 in GEnC. Besides, aPKC inhibitor treatment could activate VEGF‐VGEFR‐2 signaling in GEnC transfected with syndecan‐1 siRNA in a dose‐dependent manner. In conclusion, we speculated that phosphorylation of Dab2 is involved in preventing activation of VEGF‐VEGFR‐2 signaling in GEnC transfected with syndecan‐1 siRNA. This provides a new target for the therapy of GEnC injury and kidney disease.

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XenopusDab2 is required for embryonic angiogenesis

Abstract: Background: The molecular mechanisms governing the formation of the embryonic vascular system remain poorly understood. Here, we show that Disabled-2 (Dab2), a cytosolic adaptor protein, has a pivotal role in the blood vessel formation in Xenopus early embryogenesis.

Cited by 17 publications

References 64 publications

Disabled-2: a positive regulator of the early differentiation of myoblasts

Disabled-2: a positive regulator of the early differentiation of myoblasts

Head formation requires Dishevelled degradation that is mediated by March2 in concert with Dapper1

Phosphorylation of Dab2 is involved in inhibited VEGF‐VEGFR‐2 signaling induced by downregulation of syndecan‐1 in glomerular endothelial cell

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