On the role of glypicans in the process of morphogen gradient formation.
Glypicans are cell surface molecules that influence signaling and gradient formation of secreted morphogens and growth factors. Several distinct functions have been ascribed to glypicans including acting as co-receptors for signaling proteins. Recent data show that glypicans are also necessary for morphogen propagation in the tissue. In the present study, a model describing the interaction of a morphogen with glypicans is formulated, analyzed and compared with measurements of the effect of glypican Dally-like (Dlp) overexpression on Wingless (Wg) morphogen signaling in Drosophila melanogaster wing imaginal discs. The model explains the opposing effect that Dlp overexpression has on Wg signaling in the distal and proximal regions of the disc and makes a number of quantitative predictions for further experiments. In particular, our model suggests that Dlp acts by allowing Wg to diffuse on cell surface while protecting it from loss and degradation, and that Dlp rather than acting as Wg co-receptor competes with receptors for morphogen binding.
Hufnagel
Lars
L
Kavli Institute for Theoretical Physics, Kohn Hall, University of California, Santa Barbara, CA 93106, USA.
Kreuger
Johan
J
Cohen
Stephen M
SM
Shraiman
Boris I
BI
D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology; D004331:Drosophila melanogaster / Q000254:growth & development*; D053673:Glypicans / Q000378:metabolism / Q000502:physiology*; D006133:Growth Substances / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009024:Morphogenesis / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D011509:Proteoglycans / Q000378:metabolism / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D014921:Wings, Animal / Q000254:growth & development; D051155:Wnt1 Protein
D029721:Drosophila Proteins; D053673:Glypicans; D006133:Growth Substances; D011509:Proteoglycans; D011518:Proto-Oncogene Proteins; D051155:Wnt1 Protein; C420997:dlp protein, Drosophila; C074622:wg protein, Drosophila