title: Semaphorin signaling in cardiovascular development.
abstract: Semaphorins were originally identified as neuronal guidance molecules mediating their attractive or repulsive signals by forming complexes with plexin and neuropilin receptors. Subsequent research has identified functions for semaphorin signaling in many organs and tissues outside of the nervous system. Vital roles for semaphorin signaling in vascular patterning and cardiac morphogenesis have been demonstrated, and impaired semaphorin signaling has been associated with various human cardiovascular disorders, including persistent truncus arteriosus, sinus bradycardia and anomalous pulmonary venous connections. Here, we review the functions of semaphorins and their receptors in cardiovascular development and disease and highlight important recent discoveries in the field.
authors: Department of Cell and Developmental Biology, Cardiovascular Institute and Institute for Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104 USA. Electronic address: epsteinj@upenn.edu.
authors: Jonathan A
authors: JA
authors: Epstein
authors: Department of Cell and Developmental Biology, Cardiovascular Institute and Institute for Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104 USA.
authors: Haig
authors: H
authors: Aghajanian
authors: Program in Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical School Singapore, and the National Heart Research Institute Singapore, National Heart Center Singapore, Singapore. Electronic address: manvendra.singh@duke-nus.edu.sg.
authors: Manvendra K
authors: MK
authors: Singh
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism*; D002319:Cardiovascular System / Q000196:embryology* / Q000378:metabolism*; D006801:Humans; D039961:Semaphorins / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D039961:Semaphorins
references: Cell. 1993 Oct 22;75(2):217-27
references: 8402908
references: Circ Res. 2012 Mar 30;110(7):904-6
references: 22461359
references: J Card Fail. 2011 Sep;17(9):771-8
references: 21872148
references: Dev Biol. 1996 Mar 15;174(2):221-32
references: 8631495
references: Dev Cell. 2012 Mar 13;22(3):639-50
references: 22421048
references: Circ Res. 1991 May;68(5):1204-15
references: 2018987
references: Neuron. 2007 Feb 15;53(4):535-47
references: 17296555
references: J Cell Mol Med. 2013 May;17(5):608-16
references: 23711091
references: Nature. 2003 Jul 24;424(6947):391-7
references: 12879061
references: Sci Signal. 2012 Jan 17;5(207):ra6
references: 22253263
references: J Mol Diagn. 2013 Mar;15(2):158-70
references: 23274168
references: Dev Biol. 2008 Sep 1;321(1):251-62
references: 18625214
references: N Engl J Med. 2010 Oct 21;363(17):1638-47
references: 20961247
references: Circ J. 2012;76(7):1556-62
references: 22664784
references: FEBS Lett. 2000 Dec 1;486(1):68-72
references: 11108845
references: Semin Cell Dev Biol. 2005 Dec;16(6):704-15
references: 16054405
references: Pharmacol Ther. 2011 Jan;129(1):82-96
references: 20937304
references: Semin Cell Dev Biol. 2013 Mar;24(3):139-45
references: 23253452
references: Adv Exp Med Biol. 2002;515:81-90
references: 12613545
references: Neuron. 2011 Aug 11;71(3):460-73
references: 21835343
references: J Biomol NMR. 2005 Apr;31(4):369-70
references: 15929008
references: Nat Med. 2007 May;13(5):604-12
references: 17417650
references: Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10470-5
references: 12142468
references: J Lab Clin Med. 1985 Aug;106(2):205-10
references: 4020248
references: EMBO Rep. 2004 Jul;5(7):710-4
references: 15218527
references: Cell. 1997 Aug 22;90(4):739-51
references: 9288753
references: J Biol Chem. 2007 Dec 21;282(51):37215-24
references: 17916560
references: Arterioscler Thromb Vasc Biol. 2011 Jan;31(1):151-9
references: 20947821
references: Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):2194-9
references: 24469813
references: J Biol Chem. 1998 Mar 27;273(13):7326-31
references: 9516427
references: Trends Mol Med. 2014 Oct;20(10):589-98
references: 25154329
references: Mol Med. 2004 Jan-Jun;10(1-6):12-8
references: 15502878
references: J Cell Biol. 1999 Jul 12;146(1):233-42
references: 10402473
references: Biochemistry. 2013 Oct 29;52(43):7551-8
references: 24079887
references: J Biol Chem. 2014 Jun 27;289(26):17971-9
references: 24825896
references: Cleve Clin J Med. 2008 Mar;75 Suppl 2:S94-6
references: 18540155
references: J Biol Chem. 2011 Nov 25;286(47):41036-45
references: 21969379
references: J Clin Invest. 2011 May;121(5):1894-904
references: 21505261
references: Genes Dev. 2011 Jul 1;25(13):1399-411
references: 21724832
references: Development. 2014 Dec;141(23):4500-12
references: 25377552
references: Blood. 2011 Jun 2;117(22):6024-35
references: 21355092
references: Eur Heart J. 2011 Jun;32(12):1446-56
references: 21285074
references: Dev Dyn. 2013 May;242(5):580-90
references: 23444297
references: Novartis Found Symp. 2007;283:230-5; discussion 235-41
references: 18300426
references: Circ Res. 2000 Apr 14;86(7):816-21
references: 10764417
references: Cells Tissues Organs. 2001;169(2):89-103
references: 11399849
references: Mol Cancer. 2010 Sep 21;9:251
references: 20858260
references: Cell. 2010 Feb 19;140(4):460-76
references: 20178740
references: Am J Med Genet A. 2013 Dec;161A(12):3115-20
references: 24254849
references: Nat Med. 2013 Jun;19(6):760-5
references: 23685842
references: Nat Rev Cancer. 2008 Aug;8(8):632-45
references: 18580951
references: Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13933-8
references: 19666519
references: Mech Dev. 2001 Nov;109(1):115-9
references: 11677062
references: J Anat. 1999 Oct;195 ( Pt 3):341-57
references: 10580850
references: Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):2993-8
references: 18287072
references: Anticancer Agents Med Chem. 2011 Jun;11(5):442-7
references: 21492075
references: Dev Cell. 2011 Aug 16;21(2):301-14
references: 21802375
references: Cell. 1999 Oct 1;99(1):71-80
references: 10520995
references: Dev Cell. 2003 Jul;5(1):45-57
references: 12852851
references: Neuron. 1997 Sep;19(3):531-7
references: 9331346
references: Circulation. 1994 Apr;89(4):1697-708
references: 7908612
references: Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9504-8
references: 1409660
references: Nat Cell Biol. 2006 Jun;8(6):615-22
references: 16715077
references: Mol Cell Biol. 2005 Mar;25(6):2310-9
references: 15743826
references: Circ Res. 1998 Jun 1;82(10):1043-52
references: 9622157
references: Neuron. 1995 Jun;14(6):1189-99
references: 7605632
references: Nat Cell Biol. 2004 Dec;6(12):1204-11
references: 15543137
references: Dev Biol. 2009 Jan 1;325(1):82-93
references: 18992737
references: Elife. 2014 Sep 22;3:e03720
references: 25244320
references: J Biol Chem. 2007 Mar 2;282(9):6899-905
references: 17204469
references: Nat Rev Mol Cell Biol. 2005 Oct;6(10):789-800
references: 16314868
references: Nature. 2010 Mar 25;464(7288):549-53
references: 20336138
references: Science. 2005 Jan 14;307(5707):265-8
references: 15550623
references: J Am Coll Cardiol. 1999 Jul;34(1):233-40
references: 10400016
references: Development. 1995 Dec;121(12):4309-18
references: 8575331
references: Development. 1999 Nov;126(21):4895-902
references: 10518505
references: Neuron. 2001 Feb;29(2):429-39
references: 11239433
references: Immunity. 2005 Mar;22(3):305-16
references: 15780988
references: PLoS Genet. 2013 Apr;9(4):e1003364
references: 23593010
references: J Clin Invest. 2013 Jan;123(1):71-4
references: 23281412
references: J Clin Invest. 2010 Aug;120(8):2684-98
references: 20664171
references: Cancer Res. 2004 Feb 1;64(3):1008-15
references: 14871832
references: Circ Res. 2012 Aug 3;111(4):426-36
references: 22723300
references: Int J Mol Med. 2010 Jul;26(1):39-44
references: 20514420
references: Cell Res. 2012 Jan;22(1):23-32
references: 22157652
references: Blood. 2012 Nov 8;120(19):4104-15
references: 23007403
references: Cancer Res. 2008 Sep 1;68(17):6922-31
references: 18757406
references: Neuron. 2000 Jan;25(1):29-41
references: 10707970
references: Nat Rev Genet. 2008 Jan;9(1):49-61
references: 18071321
references: Circulation. 2000 Apr 25;101(16):1960-9
references: 10779463
references: FASEB J. 2006 Oct;20(12):2150-2
references: 16940438
references: Nat Immunol. 2010 Jul;11(7):594-600
references: 20512151
references: Neuron. 2005 Oct 6;48(1):63-75
references: 16202709
references: Circ Res. 2012 Aug 3;111(4):437-45
references: 22723296
references: J Clin Invest. 2006 Apr;116(4):929-39
references: 16557299
references: Genes Dev. 2004 Feb 15;18(4):435-47
references: 14977921
references: Cell Mol Life Sci. 2009 Feb;66(4):649-66
references: 18953684
references: Development. 2001 Aug;128(16):3071-80
references: 11688557
references: Cancer Biol Ther. 2005 Jun;4(6):659-68
references: 15917651
references: EMBO J. 2007 Mar 7;26(5):1373-84
references: 17318185
references: Development. 2002 Oct;129(20):4797-806
references: 12361971
references: Am J Pathol. 2002 Jan;160(1):289-96
references: 11786422
references: Cold Spring Harb Perspect Med. 2012 Jan;2(1):a006718
references: 22315716
references: Arterioscler Thromb Vasc Biol. 2009 Jul;29(7):1039-45
references: 19390055
references: Development. 2001 Aug;128(16):3061-70
references: 11688556
references: Neuron. 2000 Jan;25(1):43-56
references: 10707971
references: Genes Dev. 2011 Nov 15;25(22):2333-46
references: 22051878
references: Nature. 1996 Oct 10;383(6600):525-8
references: 8849723
references: Curr Med Chem. 2011;18(23):3563-75
references: 21756227
references: Proc Natl Acad Sci U S A. 2013 Jan 29;110(5):1738-43
references: 23319608
references: Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3657-62
references: 11891274
references: Dev Cell. 2004 Jul;7(1):107-16
references: 15239958
references: J Neurosci. 2003 Jul 30;23(17):6671-80
references: 12890759
references: Cell. 1998 Mar 20;92(6):735-45
references: 9529250
references: Blood. 2008 Mar 1;111(5):2674-80
references: 18180379