Opposing Activities of Dally-like Glypican at High and Low Levels of Wingless Morphogen Activity

Kreuger, Johan; Pérez, Lídia; Giráldez, Antonio J.; Cohen, Stephen M.

doi:10.1016/j.devcel.2004.08.005

Cited by 200 publications

(232 citation statements)

References 60 publications

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“…This result is consistent with earlier work showing that Dlp more strongly affects the Wg activity gradient and disk growth along the DV axis (41,42,44), whereas Dally more strongly influences Dpp (28,43). The observed dependence of disk size on Dpp profile is also consistent with the recent report on the effect of Dpp modulations (direct or via modulations of Ubx or tkv) on the size of the Drosophila haltere (45,46).…”

Section: Resultssupporting

confidence: 82%

“…We asked whether we could change disk size by modulating Dpp stability and its distribution over the wing disk by modifying the glypican matrix on the surface of disk cells. We used glypicans Dally and Dally-like (Dlp) (28,(41)(42)(43)(44), components of the proteoglycan matrix on the disk surface that are known to affect Dpp and Wg morphogen distributions. We overexpressed Dally and Dlp in the posterior compartment of the wing disk with engrailed-GAL4 and monitored Dpp signaling by using pMad antibody.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

On the mechanism of wing size determination in fly development

Hufnagel

Teleman

Rouault

et al. 2007

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

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341

372

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A fundamental and unresolved problem in animal development is the question of how a growing tissue knows when it has achieved its correct final size. A widely held view suggests that this process is controlled by morphogen gradients, which adapt to tissue size and become flatter as tissue grows, leading eventually to growth arrest. Here, we present evidence that the decapentaplegic (Dpp) morphogen distribution in the developing Drosophila wing imaginal disk does not adapt to disk size. We measure the distribution of a functional Dpp-GFP transgene and the Dpp signal transduced by phospho-Mad and show that the characteristic length scale of the Dpp profile remains approximately constant during growth. This finding suggests an alternative scenario of size determination, where disk size is determined relative to the fixed morphogen distribution by a certain threshold level of morphogen required for growth. We propose that when disk boundary reaches the threshold the arrest of cell proliferation throughout the disk is induced by mechanical stress in the tissue. Mechanical stress is expected to arise from the nonuniformity of morphogen distribution that drives growth. This stress, through a negative feedback on growth, can compensate for the nonuniformity of morphogen, achieving uniform growth with the rate that vanishes when disk boundary reaches the threshold. The mechanism is demonstrated through computer simulations of a tissue growth model that identifies the key assumptions and testable predictions. This analysis provides an alternative hypothesis for the size determination process. Novel experimental approaches will be needed to test this model. growth regulation ͉ imaginal disc ͉ mechanics

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Section: Resultssupporting

confidence: 82%

Section: Resultsmentioning

confidence: 99%

On the mechanism of wing size determination in fly development

Hufnagel

Teleman

Rouault

et al. 2007

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

Self Cite

341

372

View full text Add to dashboard Cite

show abstract

“…Notum is expressed at the DV boundary and was proposed to downregulate Wg signaling by modulating Dlp activity (Giraldez et al, 2002). During the reviewing process of this manuscript, Cohen's (Kreuger et al, 2004) and Selleck's (Kirkpatrick et al, 2004) (Kirkpatrick et al, 2004). However, on the basis of our data in this work, we suggest that Notum inhibit Wg signaling mainly by modifying Dally in the wing disc.…”

Section: Roles Of Dlp Dally and Notum In Modulating Wg Signalingcontrasting

confidence: 41%

“…Finally, it is important to mention that Notum can reduce the amount of Dally when they are co-expressed in Drosophila S2 cells (Giraldez et al, 2002), suggesting that Notum can modify Dally as well. Although Notum can shed Dlp, whether shed Dlp acts as a Wg inhibitor need to be further determined (Kreuger et al, 2004). Therefore, further experiments are necessary to define the mechanism(s) of Notum-mediated Wg inhibition.…”

Section: Roles Of Dlp Dally and Notum In Modulating Wg Signalingmentioning

confidence: 99%

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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“…Endocytosis is proposed to be less efficient basolaterally, facilitating Wg diffusion (Marois et al 2006). The Wg receptors Fz, Fz-2, and Arrow can promote Wg degradation (Han et al 2005;Piddini et al 2005), while the secreted hydrolase Notum can inhibit Wg signaling by modifying Dally and Dly (Giraldez et al 2002;Han et al 2005;Kirkpatrick et al 2004;Kreuger et al 2004).…”

Section: Getting Out and About-wnt Secretion And Transportmentioning

confidence: 99%

Wnt Signaling from Development to Disease: Insights from Model Systems

Cadigan¹,

Peifer²

2009

Cold Spring Harbor Perspectives in Biology

272

259

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One of the early surprises in the study of cell adhesion was the discovery that b-catenin plays dual roles, serving as an essential component of cadherin-based cell -cell adherens junctions and also serving as the key regulated effector of the Wnt signaling pathway. Here, we review our current model of Wnt signaling and discuss how recent work using model organisms has advanced our understanding of the roles Wnt signaling plays in both normal development and in disease. These data help flesh out the mechanisms of signaling from the membrane to the nucleus, revealing new protein players and providing novel information about known components of the pathway.

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Opposing Activities of Dally-like Glypican at High and Low Levels of Wingless Morphogen Activity

Cited by 200 publications

References 60 publications

On the mechanism of wing size determination in fly development

On the mechanism of wing size determination in fly development

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

Wnt Signaling from Development to Disease: Insights from Model Systems

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