title: The serpin PN1 is a feedback regulator of FGF signaling in germ layer and primary axis formation.
abstract: 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.
authors.affiliation: Lund Stem Cell Center, Lund University, Lund 221 84, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Acosta
authors.affiliation: Lund Stem Cell Center, Lund University, Lund 221 84, Sweden.
authors.forename: Dobromir
authors.initials: D
authors.lastname: Iliev
authors.affiliation: Lund Stem Cell Center, Lund University, Lund 221 84, Sweden.
authors.forename: Tan Hooi Min
authors.initials: TH
authors.lastname: Grahn
authors.affiliation: Lund Stem Cell Center, Lund University, Lund 221 84, Sweden.
authors.forename: Nadège
authors.initials: N
authors.lastname: Gouignard
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund 221 84, Sweden.
authors.forename: Marco
authors.initials: M
authors.lastname: Maccarana
authors.affiliation: Lund Stem Cell Center, Lund University, Lund 221 84, Sweden.
authors.forename: Julia
authors.initials: J
authors.lastname: Griesbach
authors.affiliation: Lund Stem Cell Center, Lund University, Lund 221 84, Sweden.
authors.forename: Svende
authors.initials: S
authors.lastname: Herzmann
authors.affiliation: Lund Stem Cell Center, Lund University, Lund 221 84, Sweden Department of Anatomical Sciences and Pathology, School of Medicine, Ardabil University of Medical Sciences, Ardabil 56189-53141, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Sagha
authors.affiliation: Lund Stem Cell Center, Lund University, Lund 221 84, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Climent
authors.affiliation: Lund Stem Cell Center, Lund University, Lund 221 84, Sweden edgar.pera@med.lu.se.
authors.forename: Edgar M
authors.initials: EM
authors.lastname: Pera
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D025461:Feedback, Physiological / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005855:Germ Layers / Q000196:embryology*; D015151:Immunoblotting; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D058258:Serpin E2 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014981:Xenopus / Q000196:embryology*
chemical_list: D058258:Serpin E2; D005346:Fibroblast Growth Factors
keywords: Early development; FGF; HtrA1; SerpinE2; Syndecan; Xenopus