Lisbeth Schmidt Laursen

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

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Pregnancy-associated plasma protein-A2 modulates development of cranial cartilage and angiogenesis in zebrafish embryos. / Kjaer-Sorensen, Kasper; Engholm, Ditte Høyer; Jepsen, Malene R; Morch, Maria G; Weyer, Kathrin; Hefting, Louise L; Skov, Louise L; Laursen, Lisbeth S; Oxvig, Claus.

In: Journal of Cell Science, 18.09.2014.

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@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 Ltd.",

}

RIS

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

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

ER -