Let it flow: Morpholino knockdown in zebrafish embryos reveals a pro-angiogenic effect of the metalloprotease meprin alpha2.

PloS One
Andre SchütteChristoph Becker-Pauly

Abstract

Meprin metalloproteases are thought to be involved in basic physiological functions such as cell proliferation and tissue differentiation. However, the specific functions of these enzymes are still ambiguous, although a variety of growth factors and structural proteins have been identified as meprin substrates. The discovery of meprins alpha(1), alpha(2) and beta in teleost fish provided the basis for uncovering their physiological functions by gene silencing in vivo. A Morpholino knockdown in zebrafish embryos targeting meprin alpha(1) and beta mRNA caused defects in general tissue differentiation. But meprin alpha(2) morphants were affected more specifically and showed severe failures in the formation of the vascular system provoking the hypothesis of a pro-angiogenic effect. The blood circulation was largely diminished resulting in erythrocyte accumulation. These phenotypes mimic a previously described VEGF-A morphant, revealing a possible role of meprin alpha in VEGF-A activation. Indeed, human recombinant meprin alpha processed the vascular endothelial growth factor-A (VEGF-A) specifically, revealing the same cleavage products detectable for VEGF from zebrafish whole lysate. Our results demonstrate that meprin metalloprote...Continue Reading

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Citations

Sep 19, 2012·Proceedings of the National Academy of Sciences of the United States of America·Joan L ArolasF Xavier Gomis-Rüth
Sep 4, 2012·Cellular and Molecular Life Sciences : CMLS·Tamara JeffersonChristoph Becker-Pauly
Jun 8, 2011·The Journal of Biological Chemistry·Tamara JeffersonChristoph Becker-Pauly
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Oct 31, 2015·Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution·Tatsuki NagasawaShigeki Yasumasu
Aug 14, 2013·Proceedings of the National Academy of Sciences of the United States of America·Claudia BroderChristoph Becker-Pauly
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Sep 3, 2010·Biochemistry·Jana HedrichChristoph Becker-Pauly

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Methods Mentioned

BETA
X-ray
Assay

Software Mentioned

GeneTools
TrEMBL
ImageJ

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