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

Acosta, Helena LU ; Iliev, Dobromir LU ; Tan Grahn, Hooi Min LU ; Gouignard, Nadège LU ; Maccarana, Marco LU ; Griesbach, Julia LU ; Herzmann, Svende; Sagha, Mohsen LU ; Climent, Maria LU and Pera, Edgar LU (2015) In Development 142(6). p.1146-1158
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Development
volume
142
issue
6
pages
1146 - 1158
publisher
Society for International Development
external identifiers
  • pmid:25758225
  • wos:000351697700014
  • scopus:84929515389
ISSN
1477-9129
DOI
10.1242/dev.113886
language
English
LU publication?
yes
id
1c5b7cd1-ca7c-4a48-863b-39c89ff37e83 (old id 5264761)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25758225?dopt=Abstract
date added to LUP
2015-04-02 18:51:16
date last changed
2017-02-05 03:11:59
@article{1c5b7cd1-ca7c-4a48-863b-39c89ff37e83,
  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.},
  author       = {Acosta, Helena and Iliev, Dobromir and Tan Grahn, Hooi Min and Gouignard, Nadège and Maccarana, Marco and Griesbach, Julia and Herzmann, Svende and Sagha, Mohsen and Climent, Maria and Pera, Edgar},
  issn         = {1477-9129},
  language     = {eng},
  number       = {6},
  pages        = {1146--1158},
  publisher    = {Society for International Development},
  series       = {Development},
  title        = {The serpin PN1 is a feedback regulator of FGF signaling in germ layer and primary axis formation.},
  url          = {http://dx.doi.org/10.1242/dev.113886},
  volume       = {142},
  year         = {2015},
}