A role for Syndecan-4 in neural induction involving ERK- and PKC-dependent pathways.
Syndecan-4 (Syn4) is a heparan sulphate proteoglycan that is able to bind to some growth factors, including FGF, and can control cell migration. Here we describe a new role for Syn4 in neural induction in Xenopus. Syn4 is expressed in dorsal ectoderm and becomes restricted to the neural plate. Knockdown with antisense morpholino oligonucleotides reveals that Syn4 is required for the expression of neural markers in the neural plate and in neuralised animal caps. Injection of Syn4 mRNA induces the cell-autonomous expression of neural, but not mesodermal, markers. We show that two parallel pathways are involved in the neuralising activity of Syn4: FGF/ERK, which is sensitive to dominant-negative FGF receptor and to the inhibitors SU5402 and U0126, and a PKC pathway, which is dependent on the intracellular domain of Syn4. Neural induction by Syn4 through the PKC pathway requires inhibition of PKCdelta and activation of PKCalpha. We show that PKCalpha inhibits Rac GTPase and that c-Jun is a target of Rac. These findings might account for previous reports implicating PKC in neural induction and allow us to propose a link between FGF and PKC signalling pathways during neural induction.
Kuriyama
Sei
S
Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
Mayor
Roberto
R
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D004475:Ectoderm / Q000166:cytology / Q000201:enzymology; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008954:Models, Biological; D054258:Neural Plate / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors; D053671:Syndecan-4 / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D014982:Xenopus laevis / Q000196:embryology*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D053671:Syndecan-4; D018808:Transcription Factor AP-1; D005346:Fibroblast Growth Factors; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D048049:Extracellular Signal-Regulated MAP Kinases; D010738:Type C Phospholipases; D020830:rac1 GTP-Binding Protein