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=== Wnt ===
Wnt proteins are extracellular [[growth factorsfactor]]s that activate intracellular signalling pathways. There are two types of pathways: canonical and non-canonical. The classic canonical Wnt pathway involves [[Beta-catenin|B-catenin]] protein as a signaling mediator. Wnt maintains B-catenin by preventing against [[Proteasome]] degradation. Thus, B-catenin is stabilized in the presence of Wnt and regulates gene transcription through interaction with TCF/LEF transcription factors.<ref name="Gessert (2010)"> Gessert S. and Kuhl M. [http://circres.ahajournals.org/content/107/2/186.full "The multiple phases and faces of wnt signaling during cardiac differentiation and development."] Circulation Research, 2010 107(2) p 186 - 199 doi10.1161/CIRCRESAHA.110.221531. Accessed 19 November 2012.</ref> The canonical Wnt/B-catenin pathway is important for control of cell proliferation.<ref name="Kirby (2010)2">Kirby M. L. and Hutson M. R. [http://dx.doi.org/10.4161/cam.4.4.13489 "Factors controlling cardiac neural crest cell migration."] Cell adhesion and migration, December 2010 4(4). Accessed 20 November 2012.</ref> The non-canonical Wnt pathway is independent of B-catenin and has an inhibitory effect on canonical Wnt signaling.<ref name="Gessert (2010)"/>
Wnt signaling pathways play a role in CNCC development as well as OFT development.<ref name="Gessert (2010)"/> In mice, decrease of B-catenin results in a decrease in the proliferation of CNCCs.<ref name="Gessert (2010)"/> Downregulation of the Wnt coreceptor Lrp6 leads to a reduction of CNCCs in the dorsal neural tube and in the pharyngeal arches, and results in ventricular, septal, and OFT defects.<ref name="Gessert (2010)"/> Canonical Wnt signaling is especially important for cell cycle regulation of CNCC development and the initiation of CNCC migration.<ref name="Gessert (2010)"/> Non-canonical Wnt signaling plays a greater role in promoting cardiac differentiation and OFT development.<ref name="Gessert (2010)"/>
=== Notch ===
[[Notch proteins|Notch]] is a transmembrane protein whose signaling is required for differentiation of CNCCs to vascular [[smooth muscle]] cells and for proliferation of cardiac [[myocytes]] (muscle cells of the heart). In mice, disruption of Notch signaling results in the neural crest in aortic arch branching defects and pulmonary stenosis, as well as a defect in the development of the smooth muscle cells of the sixth aortic arch artery, which is the precursor to the pulmonary artery.<ref name="Niessen (2008)">Niessen K. and Karsan A. "Notch signaling in cardiac development." Circulation Research 2008, 102 p1169 - 1181 doi 10.1161/CIRCRESAHA.108.174318 pmid18497317. Accessed 20 November 2012.</ref> In humans, mutations in Notch most often result in bicuspid aortic valve disease and calcification of the aortic valve.<ref name="Garg (2005)>Garg V. et al [http://www.nature.com/nature/journal/v437/n7056/full/nature03940.html "Mutations in NOTCH1 cause aortic valve disease." Nature September 2005 437(7056) p 270 - 274. doi 10.1038/nature03940 Accessed 20 November 2012.</ref>
=== Bone Morphogeneticmorphogenetic Proteins (BMPs)proteins ===
[[Bone morphogenetic protein]]s (BMPs) are required for neural crest cell migration into the cardiac cushions (precursors to heart valves and septa) and for differentiation of neural crest cells to smooth muscle cells of the aortic arch arteries. In neural crest–specific Alk2-deficient embryos, the cardiac cushions of the outflow tract are deficient in cells because of defects in neural crest cell migration.<ref name=Kaartinen2004"Kaartinen (2004)">{{citeKaartinen journal|last=Kaartinen|first=V|coauthors=Dudas. M,et Nagyal A, Sridurongrit S, Lu MM, Epstein JA|title="Cardiac outflow tract defects in mice lacking ALK2 in neural crest cells".|journal= Development|date= July 2004|volume=, 131|issue=(14|pages=3481–90|accessdate=19) Novemberp3481 - 3490 2012|pmid= 15226263|doi=10 doi10.1242/dev.01214}} Accessed 19 November 2012.</ref>
=== FGF8Fibroblast growth factor 8 ===
[[Fibroblast growth factor 8]] (FGF8) transcription factors are essential for regulating the addition of secondary heart field cells into the cardiac outflow tract. FGF8 mouse mutants have a range of cardiac defects including underdeveloped arch arteries and transposition of the great arteries.<ref name="Abu-Issa2002Issa (2002)">{{cite journal|last=Abu-Issa|first=Radwan|coauthors=Smyth, G,R. Smoak,et I,al Yamamura,[http://dev.biologists.org/content/129/19/4613.full.pdf+html K, & Meyers, EN|title=Fgf8"FGF8 is required for pharyngeal arch and cardiovascular development in the mouse|journal=."] Development|date= October 2012|volume= 129|pages=4613–4625|url=http://dev.biologists.org/content/129/(19/4613.full.pdf+html|accessdate=November) p4163 - 4625 Accessed 19, November 2012|issue=19}}.</ref><ref name=Frank2002>{{cite journal|last="Frank|first=DU|coauthors=Fotheringham, LK,(2002)" Brewer,> JA,Frank Muglia,D. LJ,U. Tristani-Firouzi,et M,al Capecchi, MR, Moon, AM|title=An Fgf8"FGF8 mouse mutant phenocopies human 22q11 deletion syndrome|journal=." Development|date= October 2002|volume= 129|issue=(19|pages=4591–603|accessdate=) p4591 - 4603 pmid12223415 pmc1876665. Accessed 19 November 2012|pmid=12223415|pmc=1876665}}.</ref>
=== GATA ===
[[GATA transcription factorsfactor]]s, alsowhich are complex molecules that bind to the DNA sequence ''GATA'', play a critical rolesrole in cell lineage differentiation restriction during cardiac development. WhenThe GATA-6primary isfunction inactivatedof [[GATA6]] in cardiovascular development is to regulate the CNCCsmorphogenetic itpatterning canof leadthe tooutflow tract and aortic arch. When [[GATA6]] is inactivated in CNCCs, various cardiovascular defects such as persistent truncus arteriorus and interrupted aortic arch may occur. This phenotype (anomaly) was also observed when GATA-6GATA6 was inactivated within the vascular smooth muscle cells (VSMCs).<ref name=Lepore2006>{{cite"Lepore journal|last=(2006)">Lepore|first=John J|coauthors=Mericko,. PA, Cheng, LJ., Lu,et MM,al Morrisey,[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1409743/pdf/JCI0627363.pdf EE, & Parmacek, MS|title="GATA-6 regulates semaphorin 3C and is required in cardiac neural crest for cardiovascular morphogenesis|journal=Journnal."] Journal of Clinical Investigation|date= 3 April 2006|volume=, 116|issue=(4|pages=929–939|) p929 - 939 pmid16557299 pmc 1409743 doi= 10.1172/JCI27363|url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1409743/pdf/JCI0627363.pdf|accessdate=November Accessed 19, November 2012|pmid=16557299|pmc=1409743}}.</ref> ThereforeGATA6 thein primarycombination functionwith ofWnt GATA(Wnt2-6 in cardiovascular development is to regulate the morphogenetic patterning of the outflow tract and aortic arch. It is also found that GATA6-Wnt2) also playplays a role in the development of the posterior pole of the heart (the inflow tract).<ref name=Tian2010"Tian (2010)">{{cite journal|last=Tian|first=Ying|coauthors=Yuan, LJ,Y. Goss,et AM,al Wang, T, Yang, J, Lepore, JJ, Zhou, D, Schwartz, RJ, Patel, V[http://www.,ncbi.nlm.nih.gov/pmc/articles/PMC2846539/pdf/nihms177061.pdf Cohen, ED, & Morrisey, EE|title="Characterization and Inin Vivovivo Pharmacologicalpharmacological Rescuerescue of a Wnt2-Gata6GATA6 Pathwaypathway Requiredrequired for Cardiaccardiac Inflowinflow Tracttract development."] Development|journal=Developmental Cell|date= 16 February 2010|volume= 18|issue=(2|pages=275–287|url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2846539/pdf/nihms177061.pdf|accessdate=November) 19,p275 - 287 pm 2012|pmc=2846539| pmid= 20159597|doi=10 doi10.1016/j.devcel.2010.01.008}} Accessed 19 November 2012.</ref>
== CNCCS and ischaemic heart disease ==
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