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The serpin PN1 is a feedback regulator of FGF signaling in germ layer and primary axis formation.

På svenska

Author

  • Helena Acosta
  • Dobromir Iliev
  • Hooi Min Tan Grahn
  • Nadège Gouignard
  • Marco Maccarana
  • Julia Griesbach
  • Svende Herzmann
  • Mohsen Sagha
  • Maria Climent
  • Edgar Pera

Summary, in English

Germ layer formation and primary axis development rely on Fibroblast growth factors (FGFs). In Xenopus, the secreted serine protease HtrA1 induces mesoderm and posterior trunk/tail structures by facilitating the spread of FGF signals. Here, we show that the serpin Protease nexin-1 (PN1) is transcriptionally activated by FGF signals, suppresses mesoderm and promotes head development in mRNA-injected embryos. An antisense morpholino oligonucleotide against PN1 has the opposite effect and inhibits ectodermal fate. However, ectoderm and anterior head structures can be restored in PN1-depleted embryos when HtrA1 and FGF receptor activities are diminished, indicating that FGF signals negatively regulate their formation. We show that PN1 binds to and inhibits HtrA1, prevents degradation of the proteoglycan Syndecan 4 and restricts paracrine FGF/Erk signaling. Our data suggest that PN1 is a negative-feedback regulator of FGF signaling and has important roles in ectoderm and head development.

Publishing year

2015

Language

English

Pages

1146-1158

Publication/Series

Development: For advances in developmental biology and stem cells

Volume

142

Issue

6

Document type

Journal article

Publisher

The Company of Biologists Ltd

Topic

  • Developmental Biology

Status

Published

Research group

  • Celiac Disease and Diabetes Unit
  • Matrix Biology

ISBN/ISSN/Other

  • ISSN: 1477-9129