Crossveinless-2 is required for the relocalization of Chordin protein within the vertebral field in mouse embryos.
Bone morphogenetic proteins (BMPs), as well as the BMP-binding molecules Chordin (Chd), Crossveinless-2 (CV2) and Twisted Gastrulation (Tsg), are essential for axial skeletal development in the mouse embryo. We previously reported a strong genetic interaction between CV2 and Tsg and proposed a role for this interaction in the shaping of the BMP morphogenetic field during vertebral development. In the present study we investigated the roles of CV2 and Chd in the formation of the vertebral morphogenetic field. We performed immunostainings for CV2 and Chd protein on wild-type, CV2(-/-) or Chd(-/-) mouse embryo sections at the stage of onset of the vertebral phenotypes. By comparing mRNA and protein localizations we found that CV2 does not diffuse away from its place of synthesis, the vertebral body. The most interesting finding of this study was that Chd synthesized in the intervertebral disc accumulates in the vertebral body. This relocalization does not take place in CV2(-/-) mutants. Instead, Chd was found to accumulate at its site of synthesis in CV2(-/-) embryos. These results indicate a CV2-dependent flow of Chd protein from the intervertebral disc to the vertebral body. Smad1/5/8 phosphorylation was decreased in CV2(-/-)vertebral bodies. This impaired BMP signaling may result from the decreased levels of Chd/BMP complexes diffusing from the intervertebral region. The data indicate a role for CV2 and Chd in the establishment of the vertebral morphogenetic field through the long-range relocalization of Chd/BMP complexes. The results may have general implications for the formation of embryonic organ-forming morphogenetic fields.
Zakin
Lise
L
Howard Hughes Medical Institute and Department of Biological Chemistry, University of California, Los Angeles, CA 90095-1662, USA.
Chang
Ellen Y
EY
Plouhinec
Jean-Louis
JL
De Robertis
E M
EM
D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D010641:Phenotype; D010766:Phosphorylation; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013131:Spine / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*
D055415:Bone Morphogenetic Protein 4; D002352:Carrier Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C517553:crossveinless 2 protein, mouse; C054234:chordin
Dev Biol. 2001 Apr 15;232(2):372-87
11401399
J Biol Chem. 2007 Jul 6;282(27):20002-14
17483092
Development. 2004 Jan;131(1):229-40
14660436
Development. 2000 Sep;127(18):3947-59
10952893
Dev Cell. 2002 Jan;2(1):91-101
11782317
EMBO Rep. 2005 Mar;6(3):262-7
15711536
Development. 2000 Feb;127(4):821-30
10648240
Development. 2009 Apr;136(7):1093-104
19224984
Mech Dev. 2009 Dec;126(11-12):925-41
19733655
Curr Opin Genet Dev. 2008 Aug;18(4):304-10
18590818
Nature. 2000 Jun 15;405(6788):757-63
10866189
Mol Biosyst. 2007 Jul;3(7):454-7
17579769
Development. 1988 May;103(1):69-85
3197634
Dev Cell. 2008 Jun;14(6):940-53
18539121
Mech Dev. 2008 Sep-Oct;125(9-10):832-42
18644438
Dev Biol. 2004 Mar 15;267(2):374-86
15013800
Nature. 2008 Jun 26;453(7199):1205-11
18580943
Nature. 2002 Sep 19;419(6904):304-8
12239569
Development. 2006 Mar;133(5):801-11
16439480
Dev Biol. 2010 Jan 15;337(2):405-14
19914233
Development. 2004 Nov;131(21):5309-17
15456729
Cell. 1996 Aug 23;86(4):589-98
8752213
Dev Dyn. 2007 Sep;236(9):2586-93
17685487
Curr Biol. 2010 Feb 9;20(3):R89-92
20144774
Development. 2006 Nov;133(22):4463-73
17035289
Genes Dev. 1995 Sep 1;9(17):2105-16
7657163
Mech Dev. 1995 Mar;50(1):71-83
7605753
Dev Cell. 2008 Aug;15(2):248-60
18694564
Dev Biol. 2008 Nov 1;323(1):6-18
18789316
J Cell Biol. 2009 Feb 23;184(4):597-609
19221194
Mol Cell Biol. 2003 Apr;23(8):2969-80
12665593
Development. 2005 Sep;132(18):4017-27
16123311
Science. 1981 May 29;212(4498):993-1002
17779956
Development. 2006 Jan;133(2):183-93
16368928
Development. 2003 Aug;130(15):3567-78
12810603
Dev Biol. 2005 Jun 1;282(1):70-83
15936330
Nat Rev Mol Cell Biol. 2006 Apr;7(4):296-302
16482093
Nature. 2005 Mar 10;434(7030):229-34
15759004
Cell. 2005 Mar 25;120(6):873-86
15797386
Development. 2009 Nov;136(22):3715-28
19855014
Science. 2001 Jul 6;293(5527):111-5
11441185
Annu Rev Cell Dev Biol. 2007;23:293-319
17506700
Nature. 2001 Mar 22;410(6827):475-8
11260715
Cell. 1996 Aug 23;86(4):607-17
8752215
Dev Biol. 2005 Apr 1;280(1):187-200
15766758
Development. 2001 Nov;128(22):4439-47
11714670
Biochem Biophys Res Commun. 2004 Mar 5;315(2):272-80
14766204
Cold Spring Harb Perspect Biol. 2009 Aug;1(2):a001701
20066084
PLoS Genet. 2009 Feb;5(2):e1000395
19247433
Mech Dev. 2002 Dec;119 Suppl 1:S179-84
14516682
Mech Dev. 2001 Jan;100(1):119-22
11118896
Development. 2004 Dec;131(23):5825-35
15525664
Nature. 2000 Feb 10;403(6770):658-61
10688202
Birth Defects Res C Embryo Today. 2006 Sep;78(3):224-42
17061292
Cell. 1997 Oct 31;91(3):407-16
9363949
Genes Dev. 2009 Nov 1;23(21):2551-62
19884260
Nature. 1994 Oct 6;371(6497):487-92
7935761
Proc Natl Acad Sci U S A. 1920 Nov;6(11):660-3
16576553
Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5062-7
15781876
Dev Cell. 2008 May;14(5):739-50
18477456
Development. 2004 Jan;131(2):413-24
14681194