Pregnancy-associated plasma protein-A2 modulates development of cranial cartilage and angiogenesis in zebrafish embryos

Kasper Kjaer-Sorensen; Ditte Høyer Engholm; Malene R Jepsen; Maria G Morch; Kathrin Weyer; Louise L Hefting; Louise L Skov; Lisbeth S Laursen; Claus Oxvig

doi:10.1242/jcs.152587

Pregnancy-associated plasma protein-A2 modulates development of cranial cartilage and angiogenesis in zebrafish embryos

Kasper Kjaer-Sorensen, Ditte Høyer Engholm, Malene R Jepsen, Maria G Morch, Kathrin Weyer, Louise L Hefting, Louise L Skov, Lisbeth S Laursen, Claus Oxvig

Institut for Biomedicin - Forskning og uddannelse, Syd

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

Abstract

Pregnancy-associated plasma protein-A2 (PAPP-A2, pappalysin-2) is a large metalloproteinase, known to be required for normal postnatal growth and bone development in mice. We here report the detection of zebrafish papp-a2 mRNA in chordamesoderm, notochord, and lower jaw of zebrafish (Danio rerio) embryos, and that papp-a2 knockdown embryos display broadened axial mesoderm, notochord bends, and severely reduced cranial cartilages. Genetic data link these phenotypes to insulin-like growth factor binding protein-3 (Igfbp-3) and Bmp signaling, and biochemical analysis show specific Igfbp-3 proteolysis by Papp-a2, implicating Papp-a2 in the modulation of Bmp signaling by Igfbp-3 proteolysis. Knockdown of papp-a2 additionally resulted in angiogenesis defects, strikingly similar to previous observations in embryos with mutations in components of the Notch system. Concordantly, we find that Notch signaling is modulated by Papp-a2 in vivo, and, furthermore, that PAPP-A2 is capable of modulating Notch signaling independently of its proteolytic activity in cell culture. Based on these results, we conclude that Papp-a2 modulates Bmp and Notch signaling by independent mechanisms in zebrafish embryos. In conclusion, these data link pappalysin function in zebrafish to two different signaling pathways outside the IGF system.

Originalsprog	Engelsk
Tidsskrift	Journal of Cell Science
ISSN	0021-9533
DOI	https://doi.org/10.1242/jcs.152587
Status	Udgivet - 18 sep. 2014

Adgang til dokumentet

10.1242/jcs.152587

Citationsformater

@article{2a5597bb1ddf41d08295109e65413865,

title = "Pregnancy-associated plasma protein-A2 modulates development of cranial cartilage and angiogenesis in zebrafish embryos",

abstract = "Pregnancy-associated plasma protein-A2 (PAPP-A2, pappalysin-2) is a large metalloproteinase, known to be required for normal postnatal growth and bone development in mice. We here report the detection of zebrafish papp-a2 mRNA in chordamesoderm, notochord, and lower jaw of zebrafish (Danio rerio) embryos, and that papp-a2 knockdown embryos display broadened axial mesoderm, notochord bends, and severely reduced cranial cartilages. Genetic data link these phenotypes to insulin-like growth factor binding protein-3 (Igfbp-3) and Bmp signaling, and biochemical analysis show specific Igfbp-3 proteolysis by Papp-a2, implicating Papp-a2 in the modulation of Bmp signaling by Igfbp-3 proteolysis. Knockdown of papp-a2 additionally resulted in angiogenesis defects, strikingly similar to previous observations in embryos with mutations in components of the Notch system. Concordantly, we find that Notch signaling is modulated by Papp-a2 in vivo, and, furthermore, that PAPP-A2 is capable of modulating Notch signaling independently of its proteolytic activity in cell culture. Based on these results, we conclude that Papp-a2 modulates Bmp and Notch signaling by independent mechanisms in zebrafish embryos. In conclusion, these data link pappalysin function in zebrafish to two different signaling pathways outside the IGF system.",

author = "Kasper Kjaer-Sorensen and Engholm, {Ditte H{\o}yer} and Jepsen, {Malene R} and Morch, {Maria G} and Kathrin Weyer and Hefting, {Louise L} and Skov, {Louise L} and Laursen, {Lisbeth S} and Claus Oxvig",

year = "2014",

month = sep,

day = "18",

doi = "10.1242/jcs.152587",

language = "English",

journal = "Journal of Cell Science",

issn = "0021-9533",

publisher = "The Company of Biologists",

}

TY - JOUR

T1 - Pregnancy-associated plasma protein-A2 modulates development of cranial cartilage and angiogenesis in zebrafish embryos

AU - Kjaer-Sorensen, Kasper

AU - Engholm, Ditte Høyer

AU - Jepsen, Malene R

AU - Morch, Maria G

AU - Weyer, Kathrin

AU - Hefting, Louise L

AU - Skov, Louise L

AU - Laursen, Lisbeth S

AU - Oxvig, Claus

PY - 2014/9/18

Y1 - 2014/9/18

N2 - Pregnancy-associated plasma protein-A2 (PAPP-A2, pappalysin-2) is a large metalloproteinase, known to be required for normal postnatal growth and bone development in mice. We here report the detection of zebrafish papp-a2 mRNA in chordamesoderm, notochord, and lower jaw of zebrafish (Danio rerio) embryos, and that papp-a2 knockdown embryos display broadened axial mesoderm, notochord bends, and severely reduced cranial cartilages. Genetic data link these phenotypes to insulin-like growth factor binding protein-3 (Igfbp-3) and Bmp signaling, and biochemical analysis show specific Igfbp-3 proteolysis by Papp-a2, implicating Papp-a2 in the modulation of Bmp signaling by Igfbp-3 proteolysis. Knockdown of papp-a2 additionally resulted in angiogenesis defects, strikingly similar to previous observations in embryos with mutations in components of the Notch system. Concordantly, we find that Notch signaling is modulated by Papp-a2 in vivo, and, furthermore, that PAPP-A2 is capable of modulating Notch signaling independently of its proteolytic activity in cell culture. Based on these results, we conclude that Papp-a2 modulates Bmp and Notch signaling by independent mechanisms in zebrafish embryos. In conclusion, these data link pappalysin function in zebrafish to two different signaling pathways outside the IGF system.

AB - Pregnancy-associated plasma protein-A2 (PAPP-A2, pappalysin-2) is a large metalloproteinase, known to be required for normal postnatal growth and bone development in mice. We here report the detection of zebrafish papp-a2 mRNA in chordamesoderm, notochord, and lower jaw of zebrafish (Danio rerio) embryos, and that papp-a2 knockdown embryos display broadened axial mesoderm, notochord bends, and severely reduced cranial cartilages. Genetic data link these phenotypes to insulin-like growth factor binding protein-3 (Igfbp-3) and Bmp signaling, and biochemical analysis show specific Igfbp-3 proteolysis by Papp-a2, implicating Papp-a2 in the modulation of Bmp signaling by Igfbp-3 proteolysis. Knockdown of papp-a2 additionally resulted in angiogenesis defects, strikingly similar to previous observations in embryos with mutations in components of the Notch system. Concordantly, we find that Notch signaling is modulated by Papp-a2 in vivo, and, furthermore, that PAPP-A2 is capable of modulating Notch signaling independently of its proteolytic activity in cell culture. Based on these results, we conclude that Papp-a2 modulates Bmp and Notch signaling by independent mechanisms in zebrafish embryos. In conclusion, these data link pappalysin function in zebrafish to two different signaling pathways outside the IGF system.

U2 - 10.1242/jcs.152587

DO - 10.1242/jcs.152587

M3 - Journal article

C2 - 25236600

SN - 0021-9533

JO - Journal of Cell Science

JF - Journal of Cell Science

ER -

Pregnancy-associated plasma protein-A2 modulates development of cranial cartilage and angiogenesis in zebrafish embryos

Abstract

Adgang til dokumentet

Fingeraftryk

Citationsformater