Spatial and temporal expression of heparan sulfate in mouse development regulates FGF and FGF receptor assembly.
Heparan sulfate (HS) interacts with diverse growth factors, including Wnt, Hh, BMP, VEGF, EGF, and FGF family members, and is a necessary component for their signaling. These proteins regulate multiple cellular processes that are critical during development. However, a major question is whether developmental changes occur in HS that regulate the activity of these factors. Using a ligand and carbohydrate engagement assay, and focusing on FGF1 and FGF8b interactions with FGF receptor (FR)2c and FR3c, this paper reveals global changes in HS expression in mouse embryos during development that regulate FGF and FR complex assembly. Furthermore, distinct HS requirements are identified for both complex formation and signaling for each FGF and FR pair. Overall, these results suggest that changes in HS act as critical temporal regulators of growth factor and morphogen signaling during embryogenesis.
Allen
Benjamin L
BL
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53706, USA.
Rapraeger
Alan C
AC
D000818:Animals; D021461:Animals, Outbred Strains; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D016466:CHO Cells; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism / Q000494:pharmacology; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000378:metabolism* / Q000494:pharmacology; D006497:Heparan Sulfate / Q000378:metabolism*; D051379:Mice / Q000196:embryology / Q000378:metabolism*; D011247:Pregnancy; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000187:drug effects / Q000502:physiology; D011505:Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D013997:Time Factors
D016220:Fibroblast Growth Factor 1; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D006497:Heparan Sulfate; D011505:Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor; C496457:Fgf8 protein, mouse; C496366:Fgfr3 protein, mouse