Mtmr8 is essential for vasculature development in zebrafish embryos.
BACKGROUND
Embryonic morphogenesis of vascular and muscular systems is tightly coordinated, and a functional cooperation of Mtmr8 with PI3K in actin filament modeling and muscle development has been revealed in zebrafish. Here, we attempt to explore the function of Mtmr8 in vasculature development parallel to its function in muscle development.


RESULTS
During early stage of somitogenesis, mtmr8 expression was detected in both somitic mesodem and ventral mesoderm. Knockdown of mtmr8 by morpholino impairs arterial endothelial marker expression, and results in endothelial cell reduction and vasculogenesis defects, such as retardation in intersegmental vessel development and interruption of trunk dorsal aorta. Moreover, mtmr8 morphants show loss of arterial endothelial cell identity in dorsal aorta, which is effectively rescued by low concentration of PI3K inhibitor, and by over-expression of dnPKA mRNA or vegf mRNA. Interestingly, mtmr8 expression is up-regulated when zebrafish embryos are treated with specific inhibitor of Hedgehog pathway that abolishes arterial marker expression.


CONCLUSIONS
These data indicate that Mtmr8 is essential for vasculature development in zebrafish embryos, and may play a role in arterial specification through repressing PI3K activity. It is suggested that Mtmr8 should represent a novel element of the Hedgehog/PI3K/VEGF signaling cascade that controls arterial specification.
Mei
Jie
J
State Key Laboratory of Freshwater Ecology and Biotechnology, Center for Developmental Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Wuhan 430072, China.
Liu
Sha
S
Li
Zhi
Z
Gui
Jian-Fang
JF
D000818:Animals; D001808:Blood Vessels / Q000196:embryology*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism*; D038081:Organogenesis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000378:metabolism*; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000378:metabolism*
D053823:Hedgehog Proteins; D042461:Vascular Endothelial Growth Factor A; D029961:Zebrafish Proteins; D019869:Phosphatidylinositol 3-Kinases; C541683:Mtmr8 protein, zebrafish; D054558:Protein Tyrosine Phosphatases, Non-Receptor
PLoS One. 2009;4(3):e4979
19325702
Nat Med. 2002 Sep;8(9):995-1003
12185361
Blood. 2009 Jan 29;113(5):1184-91
18927432
Dev Biol. 2008 Jul 15;319(2):273-84
18514183
Curr Biol. 2006 Jul 11;16(13):1366-72
16824925
Angiogenesis. 2008;11(1):71-7
18301996
J Clin Invest. 2002 Oct;110(7):933-41
12370271
EMBO J. 1998 Jul 15;17(14):4029-45
9670018
Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1749-53
10677529
Nat Genet. 1998 Apr;18(4):303-5
9537407
Dev Cell. 2002 Jul;3(1):127-36
12110173
Genes Dev. 2006 Jun 15;20(12):1651-66
16778080
Angiogenesis. 1999;3(4):353-9
14517415
Dev Biol. 2007 Apr 15;304(2):735-44
17306248
Diabetes. 2007 Oct;56(10):2449-56
17623817
Cancer Cell. 2002 Apr;1(3):257-67
12086862
Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4622-7
11274365
Blood. 2007 Nov 15;110(10):3627-36
17698971
Arterioscler Thromb Vasc Biol. 2005 Nov;25(11):2246-54
16123328
Dev Cell. 2004 Jul;7(1):117-23
15239959
Nat Rev Mol Cell Biol. 2006 May;7(5):359-71
16633338
Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2439-44
18268319
J Biol Chem. 1999 Jun 4;274(23):16349-54
10347193
Dev Dyn. 2005 Dec;234(4):911-21
16193492
Nat Protoc. 2008;3(1):59-69
18193022
EMBO Rep. 2007 Oct;8(10):920-4
17906673
Blood. 2005 May 1;105(9):3502-11
15644413
Trends Cardiovasc Med. 2004 Nov;14(8):308-13
15596107
Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4505-10
16537363
PLoS Genet. 2009 Feb;5(2):e1000372
19197364
Dev Biol. 2001 Feb 15;230(2):278-301
11161578
Development. 2001 Oct;128(19):3675-83
11585794
Methods. 2001 Dec;25(4):402-8
11846609
Development. 2003 Nov;130(21):5281-90
12954720
J Cell Biol. 2008 Apr 21;181(2):381-94
18426981
PLoS One. 2009 Sep 30;4(9):e7261
19789708
J Cell Biol. 2004 Nov 22;167(4):711-21
15557122
J Biol Chem. 1998 Nov 13;273(46):30336-43
9804796
Mech Dev. 2000 Feb;90(2):237-52
10640707