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

Acosta, Helena ; Iliev, Dobromir ; Grahn, Tan Hooi Min ; Gouignard, Nadège ; Maccarana, Marco ; Griesbach, Julia ; Herzmann, Svende ; Sagha, Mohsen ; Climent, Maria (Universidad de Zaragoza) ; Pera, Edgar M.

Resumen: 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.

Idioma: Inglés

DOI: 10.1242/dev.113886

Año: 2015

Publicado en: Development (Cambridge, England) 142, 6 (2015), 1146-1158
ISSN: 1477-9129

Factor impacto JCR: 6.059 (2015)

Categ. JCR: DEVELOPMENTAL BIOLOGY rank: 4 / 41 = 0.098 (2015) - Q1 - T1

Factor impacto SCIMAGO: 5.235 - Molecular Biology (Q1) - Developmental Biology (Q1)

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Anatom.Anatom.Patológ.Com (Dpto. Anatom.,Embri.Genét.Ani.)

Dataset asociado: The serpin PN1 is a feedback regulator of FGF signaling in germ layer and primary axis formation ( 10.1242/dev.113886)