Increased Wnt levels in the neural tube impair the function of adherens junctions during neurulation

Shariatmadari, Maria; Peyronnet, Julie; Papachristou, Panagiotis; Horn, Zachi; Sousa, Kyle M.; Arenas, Ernest; Ringstedt, Thomas

doi:10.1016/j.mcn.2005.08.008

Cited by 18 publications

(17 citation statements)

References 63 publications

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“…We conclude that the nestin-Vangl2 embryos display an impaired cranial neurulation, a phenotype similar to that of nestinWnt7a transgenic embryos. This is in line with the effects of Wnt7a being partly mediated by Vangl2, as we have suggested previously (Shariatmadari et al, 2005).…”

Section: Cranial Neurulation Is Impaired In Nestin-vangl2 Embryossupporting

confidence: 93%

“…In order to test the effects of Vangl2 overexpression in vivo, a nestinVangl2 construct vector that directs the expression of Vangl2 to neural stem cells was generated as previously described (Shariatmadari et al, 2005). Transgenic mouse embryos obtained from pronuclear injections of nestin-Vangl2 were analyzed at embryonic day (E) 8.5 and 9.5.…”

Section: Cranial Neurulation Is Impaired In Nestin-vangl2 Embryosmentioning

confidence: 99%

“…Consortium (LLNL) cDNA CloneID 6509008 (Lennon et al, 1996)] purchased from RZPD (www.rzpd.de; RZPD CloneID IMAGp998J1714075Q3). It was then inserted into the XhoI and/or HindIII site of the pcDNA3-HA expression vector or the NotI site of the human nestin (hnestin) 1852 vector (Lothian and Lendahl, 1997;Shariatmadari et al, 2005). The (human) Vangl2-EGFP and Vangl2D4-EGFP constructs were kind gifts from Lelita T. Braiterman (Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD) (Kallay et al, 2006).…”

Section: Generation Of the Vangl2-ha And Nestin-vangl2 Constructsmentioning

confidence: 99%

“…We have previously reported that adherens junctions are disrupted in transgenic mouse embryos overexpressing Wnt7a in the developing neural tube (Shariatmadari et al, 2005). The expression of Vangl2 mRNA was increased in mouse embryos overexpressing Wnt7a, which led us to speculate that the Wnt7a-induced effect is at least partly mediated by Vangl2 and Wnt/PCP signaling.…”

Section: Introductionmentioning

confidence: 96%

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Vang-like protein 2 and Rac1 interact to regulate adherens junctions

Lindqvist¹,

Horn²,

Bryja

et al. 2010

Journal of Cell Science

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The Wnt planar cell polarity (Wnt/PCP) pathway signals through small Rho-like GTPases to regulate the cytoskeleton. The core PCP proteins have been mapped to the Wnt/PCP pathway genetically, but the molecular mechanism of their action remains unknown. Here, we investigate the function of the mammalian PCP protein Vang-like protein 2 (Vangl2). RNAi knockdown of Vangl2 impaired cell-cell adhesion and cytoskeletal integrity in the epithelial cell lines HEK293T and MDCK. Similar effects were observed when Vangl2 was overexpressed in HEK293T, MDCK or C17.2 cells. The effects of Vangl2 overexpression could be blocked by knockdown of the small GTPase Rac1 or by dominant-negative Rac1. In itself, knockdown of Rac1 impaired cytoskeletal integrity and reduced cell-cell adhesion. We found that Vangl2 bound and re-distributed Rac1 within the cells but did not alter Rac1 activity. Moreover, both transgenic mouse embryos overexpressing Vangl2 in neural stem cells and loop-tail Vangl2 loss-of-function embryos displayed impaired adherens junctions, a cytoskeletal unit essential for neural tube rigidity and neural tube closure. In vivo, Rac1 was re-distributed within the cells in a similar way to that observed by us in vitro. We propose that Vangl2 affects cell adhesion and the cytoskeleton by recruiting Rac1 and targeting its activity in the cell to adherens junctions.

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Section: Cranial Neurulation Is Impaired In Nestin-vangl2 Embryossupporting

confidence: 93%

Section: Cranial Neurulation Is Impaired In Nestin-vangl2 Embryosmentioning

confidence: 99%

Section: Generation Of the Vangl2-ha And Nestin-vangl2 Constructsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

See 2 more Smart Citations

Vang-like protein 2 and Rac1 interact to regulate adherens junctions

Lindqvist¹,

Horn²,

Bryja

et al. 2010

Journal of Cell Science

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“…It was recently reported that Wnt7a overexpression in the neural tube results in defective adherens junctions, with subsequent abnormalities in spinal neurulation (Shariatmadari et al, 2005). During zebrafish gastrulation, Wnt11 is required to modulate the cell surface localization of E-cadherin via a pathway involving the small GTPase Rab5, which regulates endocytosis (Ulrich et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Wingless signaling modulates cadherin-mediated cell adhesion inDrosophilaimaginal disc cells

Wodarz

Stewart

Nelson

et al. 2006

Journal of Cell Science

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Armadillo, the Drosophila homolog of β-catenin, plays a crucial role in both the Wingless signal transduction pathway and cadherin-mediated cell-cell adhesion, raising the possibility that Wg signaling affects cell adhesion. Here, we use a tissue culture system that allows conditional activation of the Wingless signaling pathway and modulation of E-cadherin expression levels. We show that activation of the Wingless signaling pathway leads to the accumulation of hypophosphorylated Armadillo in the cytoplasm and in cellular processes, and to a concomitant reduction of membrane-associated Armadillo. Activation of the Wingless pathway causes a loss of E-cadherin from the cell surface, reduced cell adhesion and increased spreading of the cells on the substratum. After the initial loss of E-cadherin from the cell surface, E-cadherin gene expression is increased by Wingless. We suggest that Wingless signaling causes changes in Armadillo levels and subcellular localization that result in a transient reduction of cadherin-mediated cell adhesion, thus facilitating cell shape changes, division and movement of cells in epithelial tissues.

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Strain‐specific modifier genes governing craniofacial phenotypes

Mukhopadhyay¹,

Brock²,

Webb³

et al. 2012

Birth Defects Research

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BACKGROUND The presence of strain-specific modifier genes is known to modulate the phenotype and pathophysiology of mice harboring genetically engineered mutations. Thus, identification of genetic modifier genes is requisite to understanding control of phenotypic expression. c-Ski is a transcriptional regulator. Ski−/− mice on a C57BL6J (B6) background exhibit facial clefting, while Ski−/− mice on a 129P3 (129) background present with exencephaly. METHODS In the present study, oligonucleotide-based gene expression profiling was utilized to identify potential strain-specific modifier gene candidates present in wild-type mice of B6 and 129 genetic backgrounds. Changes in gene expression were verified by TaqMan quantitative real-time PCR. RESULTS Steady-state levels of 89 genes demonstrated a significantly higher level of expression, and those of 68 genes demonstrated a significantly lower level of expression in the developing neural tubes from E8.5, B6 embryos when compared to expression levels in neural tubes derived from E8.5, 129 embryos. CONCLUSIONS Based on the results from the current comparative microarray study, and taking into consideration a number of relevant published reports, several potential strain-specific gene candidates, likely to modify the craniofacial phenotypes in various knockout mouse models have been identified.

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Increased Wnt levels in the neural tube impair the function of adherens junctions during neurulation

Cited by 18 publications

References 63 publications

Vang-like protein 2 and Rac1 interact to regulate adherens junctions

Vang-like protein 2 and Rac1 interact to regulate adherens junctions

Wingless signaling modulates cadherin-mediated cell adhesion inDrosophilaimaginal disc cells

Strain‐specific modifier genes governing craniofacial phenotypes

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