Drosophila Dpp morphogen movement is independent of dynamin-mediated endocytosis but regulated by the glypican members of heparan sulfate proteoglycans.
The Drosophila transforming growth factor beta (TGF-beta) homolog Decapentaplegic (Dpp) acts as a morphogen that forms a long-range concentration gradient to direct the anteroposterior patterning of the wing. Both planar transcytosis initiated by Dynamin-mediated endocytosis and extracellular diffusion have been proposed for Dpp movement across cells. In this work, we found that Dpp is mainly extracellular, and its extracellular gradient coincides with its activity gradient. We demonstrate that a blockage of endocytosis by the dynamin mutant shibire does not block Dpp movement but rather inhibits Dpp signal transduction, suggesting that endocytosis is not essential for Dpp movement but is involved in Dpp signaling. Furthermore, we show that Dpp fails to move across cells mutant for dally and dally-like (dly), two Drosophila glypican members of heparin sulfate proteoglycan (HSPG). Our results support a model in which Dpp moves along the cell surface by restricted extracellular diffusion involving the glypicans Dally and Dly.
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Tatyana Y
TY
Belenkaya
Chun
C
Han
Dong
D
Yan
Robert J
RJ
Opoka
Marat
M
Khodoun
Hongzhu
H
Liu
Xinhua
X
Lin
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D019521:Body Patterning; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000196:embryology* / Q000502:physiology; D034281:Dynamins / Q000235:genetics / Q000378:metabolism*; D004628:Embryonic Structures / Q000166:cytology / Q000502:physiology*; D004705:Endocytosis / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014921:Wings, Animal / Q000166:cytology / Q000196:embryology / Q000378:metabolism
D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D011993:Recombinant Fusion Proteins; C098128:dally protein, Drosophila; C420997:dlp protein, Drosophila; C064196:dpp protein, Drosophila; D034281:Dynamins; C439628:shi protein, Drosophila