The secreted serine protease xHtrA1 stimulates long-range FGF signaling in the early Xenopus embryo.
We found that the secreted serine protease xHtrA1, expressed in the early embryo and transcriptionally activated by FGF signals, promotes posterior development in mRNA-injected Xenopus embryos. xHtrA1 mRNA led to the induction of secondary tail-like structures, expansion of mesoderm, and formation of ectopic neurons in an FGF-dependent manner. An antisense morpholino oligonucleotide or a neutralizing antibody against xHtrA1 had the opposite effects. xHtrA1 activates FGF/ERK signaling and the transcription of FGF genes. We show that Xenopus Biglycan, Syndecan-4, and Glypican-4 are proteolytic targets of xHtrA1 and that heparan sulfate and dermatan sulfate trigger posteriorization, mesoderm induction, and neuronal differentiation via the FGF signaling pathway. The results are consistent with a mechanism by which xHtrA1, through cleaving proteoglycans, releases cell-surface-bound FGF ligands and stimulates long-range FGF signaling.
Department of Developmental Biochemistry, Institute of Biochemistry and Cell Biology, Georg August University Göttingen, 37077 Göttingen, Germany.
Shirui
S
Hou
Marco
M
Maccarana
Tan H
TH
Min
Ina
I
Strate
Edgar M
EM
Pera
D000818:Animals; D001483:Base Sequence; D058578:Biglycan; D019521:Body Patterning / Q000187:drug effects; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D003871:Dermatan Sulfate / Q000494:pharmacology; D004475:Ectoderm / Q000187:drug effects / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000201:enzymology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D051524:Fibroblast Growth Factor 8 / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D053673:Glypicans / Q000378:metabolism; D006497:Heparan Sulfate / Q000494:pharmacology; D006801:Humans; D008648:Mesoderm / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011509:Proteoglycans / Q000378:metabolism; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D053671:Syndecan-4 / Q000378:metabolism; D013623:Tail / Q000033:anatomy & histology / Q000187:drug effects / Q000196:embryology; D029867:Xenopus Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000378:metabolism*
D058578:Biglycan; D003871:Dermatan Sulfate; D016326:Extracellular Matrix Proteins; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D053673:Glypicans; D006497:Heparan Sulfate; D011509:Proteoglycans; D012697:Serine Endopeptidases; D053671:Syndecan-4; D029867:Xenopus Proteins; C546884:BGN protein, human; C522595:high-temperature requirement factor A1, Xenopus