Heparan Sulfate Proteoglycans are critical for the organization of the extracellular distribution of Wingless

Baeg, Gyeong-Hun; Lin, Xinhua; Perrimon, Norbert

doi:10.1042/bst029a010c

Cited by 160 publications

(267 citation statements)

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“…We have previously shown that Dally plays a role in Wg signaling in the wing disc (Lin and Perrimon, 1999). Furthermore, overexpression of Dlp leads to enhanced extracellular Wg levels in the wing disc (Baeg et al, 2001). Together, these studies implicate possible roles of Dally and Dlp in Wg gradient formation; however, their functions and mechanisms in Wg gradient formation have not been examined by loss-offunction study.…”

Section: Introductionmentioning

confidence: 74%

“…dally P2 is a dally-lacZ line used to visualize dally expression (Nakato et al, 1995). The following UAS constructs were used to overexpress the corresponding transgenes in the posterior compartment of the wing disc: UAS-dlp (Baeg et al, 2001), UAS-dally (Tsuda et al, 1999), UAS-fz and UAS-fz2 (Zhang and Carthew, 1998), and UAS-gfp-arr. UAS-gfp-arr contains the Wg signal peptide (amino acids 1-37) followed by GFP protein and six Myc tags fused with Arr in which the signal peptide (amino acids 1-54) of Arr is deleted.…”

Section: Fly Strainsmentioning

confidence: 99%

“…Extracellular Wg staining was performed as described (Baeg et al, 2001;Strigini and Cohen, 2000). Primary antibodies were used at the following dilutions: mouse anti-Wg 4D4 at 1:3 (Iowa Developmental Studies Hybridoma Bank; IDSHB), rat anti-Ci (1:10) (Motzny and Holmgren, 1995), rabbit anti-β-gal at 1:500 (Cappel), mouse anti-β-gal at 1:3000 (Roche Molecular Biochemicals), mouse anti-Dlp at 1:50 (Lum et al, 2003), rabbit anti-Wg at 1:500 (Reichsman et al, 1996), mouse antiHnt at 1:50 (IDSHB), guinea pig anti-Hrs (full-length) at 1:200 (Lloyd et al, 2002) and rabbit anti-GFP Alexa Fluor 488 at 1:1000 (Molecular Probes).…”

Section: Antibodies and Immunofluorescencementioning

confidence: 99%

“…Our recent studies have demonstrated that both Dally and Dlp are required for Hh and Dpp movement through a restricted diffusion mechanism (Belenkaya et al, 2004;Han et al, 2004b). Regarding Wg morphogen formation, several studies have shown that mutations in genes involved in HS biosynthesis lead to defects in Wg distribution in the wing disc (Baeg et al, 2001;Bornemann et al, 2004;Han et al, 2004a;Luders et al, 2003;Takei et al, 2004). We have previously shown that Dally plays a role in Wg signaling in the wing disc (Lin and Perrimon, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…Glypicans represent the main cell-surface HSPGs that are linked to the plasma membrane by a glycosyl phosphatidylinositol (GPI) linker. Drosophila has two glypican members, Division abnormally delayed (Dally) and Dally-like protein (Dlp) (Baeg et al, 2001;Khare and Baumgartner, 2000;Nakato et al, 1995). Our recent studies have demonstrated that both Dally and Dlp are required for Hh and Dpp movement through a restricted diffusion mechanism (Belenkaya et al, 2004;Han et al, 2004b).…”

Section: Introductionmentioning

confidence: 99%

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Drosophilaglypicans Dally and Dally-like shape the extracellular Wingless morphogen gradient in the wing disc

et al. 2005

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Drosophila Wingless (Wg) is the founding member of the Wnt family of secreted proteins. During the wing development, Wg acts as a morphogen whose concentration gradient provides positional cues for wing patterning. The molecular mechanism(s) of Wg gradient formation is not fully understood. Here,we systematically analyzed the roles of glypicans Dally and Dally-like protein(Dlp), the Wg receptors Frizzled (Fz) and Fz2, and the Wg co-receptor Arrow(Arr) in Wg gradient formation in the wing disc. We demonstrate that both Dally and Dlp are essential and have different roles in Wg gradient formation. The specificities of Dally and Dlp in Wg gradient formation are at least partially achieved by their distinct expression patterns. To our surprise,although Fz2 was suggested to play an essential role in Wg gradient formation by ectopic expression studies, removal of Fz2 activity does not alter the extracellular Wg gradient. Interestingly, removal of both Fz and Fz2, or Arr causes enhanced extracellular Wg levels, which is mainly resulted from upregulated Dlp levels. We further show that Notum, a negative regulator of Wg signaling, downregulates Wg signaling mainly by modifying Dally. Last, we demonstrate that Wg movement is impeded by cells mutant for both dally and dlp. Together, these new findings suggest that the Wg morphogen gradient in the wing disc is mainly controlled by combined actions of Dally and Dlp. We propose that Wg establishes its concentration gradient by a restricted diffusion mechanism involving Dally and Dlp in the wing disc.

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Section: Introductionmentioning

confidence: 74%

Section: Fly Strainsmentioning

confidence: 99%

Section: Antibodies and Immunofluorescencementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Drosophilaglypicans Dally and Dally-like shape the extracellular Wingless morphogen gradient in the wing disc

et al. 2005

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Temporal Changes in Expression of FoxA1 and Wnt7A in Isolated Adult Human Alveolar Epithelial Cells Enhanced by Heparin

Apparao

Newman

Zhang

et al. 2010

The Anatomical Record

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Pre- and postnatal developmental studies of the lung have provided compelling evidence demonstrating multiple factors that orchestrate alveolar epithelial cell differentiation. The extent to which reactivation of certain developmental pathways in the adult might influence the course of differentiation of alveolar type 2 cells (AT2) into AT1 cells is not known. In this study, we examined selected members of the forkhead (Fox) family of transcription factors and the Wnt (wingless) family of signaling proteins for expression during human alveolar cell differentiation in vitro and determined their potential responses to sulfated components of extracellular matrix (ECM), like those shed from cell surfaces or found in basement membrane and modeled by heparin. Isolated adult human AT2 cells cultured over a nine day period were used to define the temporal profile of expression of targeted factors during spontaneous differentiation to AT1 cells. FoxA1 protein was up-regulated at early to intermediate time points, where it was strongly elevated by heparin. Gene expression of Wnt7A increased dramatically beginning on day 3 and was enhanced even further on days 7 and 9 by heparin, while protein expression appeared at days 7 and 9. These temporal changes of expression suggest that sulfated ECMs may act to enhance the increase in FoxA1 at the critical juncture when AT2 cells commence the differentiation process to AT1 cells, in addition to enhancing the increase in Wnt7A when the AT1 cell phenotype stabilizes. Collectively, these factors may act to modulate differentiation and stabilize cell numbers in the adult human pulmonary alveolus.

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Frizzled‐related protein variants are risk factors for hip osteoarthritis

Lane

Lian

Nevitt

et al. 2006

Arthritis & Rheumatism

121

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Objective. To examine the association of the Arg200Trp and Arg324Gly variants of FRZB with the risk and phenotype of radiographic osteoarthritis (OA) of the hip and serum levels of Frizzled-related protein (FRP) in a prospective cohort of elderly Caucasian women.Methods. Radiographic hip OA status of patients was defined by the presence of severe joint space narrowing (JSN) (feature grade >3), a summary grade >3, or definite osteophytes (grade >2) and JSN (grade >2) in the same hip. Genotypes were obtained in 569 patients with radiographic OA of the hip and in 1,317 and 4,136 controls for the Arg200Trp and Arg324Gly variants, respectively. Serum FRP levels were measured by enzyme-linked immunosorbent assay. Multivariate logistic regression was performed.Results. The minor allele frequency for the Arg200Trp polymorphism was 0.12 in the control group compared with 0.14 in the group with radiographic OA of the hip (P ‫؍‬ 0.12), and the minor allele frequency for the Arg324Gly variant was 0.083 in the control group compared with 0.088 in the group with radiographic OA of the hip (P ‫؍‬ 0.63). The multilocus genotypes available in 1,886 subjects suggested that inheritance of both minor alleles was a risk factor for developing OA characterized by JSN (P < 0.01). Patients with radiographic OA of the hip who were homozygous for the Arg200Trp minor allele had higher serum FRP levels than controls who were homozygous for the major allele.Conclusion. Our data confirm findings of another study, that a rare haplotype with both Arg200Trp and Arg324Gly FRZB variants contributes to the genetic susceptibility to hip OA among Caucasian women, and that these polymorphisms may contribute to increased serum levels of proteins as biomarkers of OA.

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Heparan Sulfate Proteoglycans are critical for the organization of the extracellular distribution of Wingless

Abstract: SUMMARYHeparan sulfate proteoglycans are critical for the organization of the extracellular distribution of Wingless

Cited by 160 publications

References 29 publications

Drosophilaglypicans Dally and Dally-like shape the extracellular Wingless morphogen gradient in the wing disc

Drosophilaglypicans Dally and Dally-like shape the extracellular Wingless morphogen gradient in the wing disc

Temporal Changes in Expression of FoxA1 and Wnt7A in Isolated Adult Human Alveolar Epithelial Cells Enhanced by Heparin

Frizzled‐related protein variants are risk factors for hip osteoarthritis

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