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XB-ART-50200
Development March 15, 2015; 142 (6): 1146-58.

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

Acosta H , Iliev D , Grahn TH , Gouignard N , Maccarana M , Griesbach J , Herzmann S , Sagha M , Climent M , Pera EM .


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.

PubMed ID: 25758225
Article link: Development

Genes referenced: cdx4 dnph1 en2 fgf8 foxg1 foxi1 gsc htra1 htt ism1 mapk1 nkx2-5 nodal3.1 nppa otx2 pcdh8 prss1 rax serpine2 sox17a szl tbl1x tbx2 tbxt tubb2b ventx2.2
Morpholinos: htra1 MO1 serpine2 MO1 serpine2 MO2 serpine2 MO3


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