Cardiac neural crest: Difference between revisions

Revision as of 00:11, 22 December 2013

Revision as of 19:22, 15 January 2014

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[[Neural crest]] cells are a group of temporary, [[Cell potency#Multipotency|multipotent]] (can give rise to some other types of cells but not all) cells that are pinched off during the formation of the [[neural tube]] (precursor to the [[spinal cord]] and brain) and therefore are found at the dorsal (top) region of the neural tube during development.<ref name ="kirby1987">{{cite journal|last=Kirby|first=M|title=Cardiac Morphogenesis--Recent Research Advances|journal=Pediatric Research|year=1987|volume=21|issue=3|pages=219–224|url=http://www.nature.com/pr/journal/v21/n3/pdf/pr198744a.pdf}}</ref> They are derived from the [[ectoderm]] germ layer, but are sometimes called the fourth germ layer because they are so important and give rise to so many other types of cells.<ref name="kirby1987" /><ref name= "gilbert">{{cite book|last=Gilbert|first=S.F.|title=Developmental Biology|year=2010|publisher=Sinauer Associates|___location=MA|pages=373–389|url=http://www.ncbi.nlm.nih.gov/books/NBK10065/}}</ref> They migrate throughout the body and create a large number of differentiated cells such as [[neuron]]s, glial cells, pigment-containing cells in skin, skeletal tissue cells in the head, and many more.<ref name="kirby1987" /><ref name="gilbert" />

Cardiac neural crest cells (CNCCs) are a type of neural crest cells that migrate to the circumpharyngeal ridge (an arc-shape ridge above the [[pharyngeal arch]]es) and then into the 3rd, 4th and 6th pharyngeal arches and the cardiac outflow tract (OFT).<ref name="kirby1987" /><ref name="gilbert" /><ref name= "kur">{{cite journal|last=Kuratani|first=S.C.|coauthors=Kirby, M.L.|title=Migration and distribution of circumpharyngeal crest cells in the chick embryo. Formation of the circumpharyngeal ridge and E/C8+ crest cells in the vertebrate head region|journal=Anat. Rec.|yeardate=Oct 1992|month=Oct|volume=234|issue=2|pages=263–268|pmid=1384396|doi=10.1002/ar.1092340213}}</ref> They extend from the [[otic placode]]s (the structure in developing embryos that will later form the ears) to the third [[somite]]s (clusters of [[mesoderm]] that will become skeletal muscle, vertebrae and dermis).<ref name="kirby1987" /><ref name="gilbert" />

The cardiac neural crest cells:<ref name="kirby1987" /><ref name="gilbert" />

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=== Induction ===

The progenitors, or the cells that will become, CNCCs are found in the epiblast around Henson’s node.<ref name="kur" /><ref name = "kirby2010">{{cite journal|last=Kirby|first=M.K.|coauthors=Hutson, M.R.|title=Factors controlling cardiac neural crest cell migration|journal=Cell Adhesion and Migration|yeardate=December 2010|month=December|volume=4|issue=4|pages=609–621|url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3011257/pdf/cam0404_0609.pdf|pmc=3011257|pmid=20890117}}</ref> The progenitors are brought into the neural folds and signaling from molecules Wnt, FGF and BMP help induce the progenitors to become CNCCs.<ref name="kur" /><ref name="kirby2010" /> Not a lot is known about the signaling cascades that occur for neural crest induction, but it is known that an intermediate level of BMP is needed, too high or low causes the cells not to migrate.<ref name="kirby2010" />

=== Initial Migration ===

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=== Wnt ===

Wnt proteins are extracellular growth factors that activate different intracellular signaling branches.<ref name="gessert">{{cite journal|last=Gessert|first=S|coauthors=Kuhl M|title=The multiple phases and faces of wnt signaling during cardiac differentiation and development.|journal=Circulation Research|year=2010|volume=107|pages=186–199|doi=10.1161/CIRCRESAHA.110.221531|url=http://circres.ahajournals.org/content/107/2/186.full|accessdate=19 November 2012|issue=2}}</ref> There are two types of pathways: canonical and non-canonical.<ref name="gessert" /> The classic canonical Wnt pathway involves [[Beta-catenin|B-catenin]] protein as a signaling mediator.<ref name="gessert" /> Wnt maintains B-catenin by preventing against [[Proteasome]] degradation.<ref name="gessert" /> Thus, B-catenin is stabilized in the presence of Wnt and regulates gene transcription through interaction with TCF/LEF transcription factors.<ref name="gessert" /> The canonical Wnt/B-catenin pathway is important for Proliferation|cell proliferation control.<ref name="kirby2010">{{cite journal|last=Kirby|first=ML|coauthors=Hutson MR|title=Factors controlling cardiac neural crest cell migration|journal=Cell adhesion and migration|yeardate=December 2010|month=December|volume=4|issue=4|doi=http://dx.doi.org/10.4161/cam.4.4.13489|accessdate=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" />

Wnt signaling pathways play a role in CNCC development as well as OFT development.<ref name="gessert" /> In mice, decrease of B-catenin results in a decrease in the proliferation of CNCCs.<ref name="gessert" /> 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" /> Canonical Wnt signaling is especially important for cell cycle regulation of CNCC development and the initiation of CNCC migration.<ref name="gessert" /> Non-canonical Wnt signaling plays a greater role in promoting cardiac differentiation and OFT development.<ref name="gessert" />

=== Notch ===

Notch signaling is required for differentiation of CNCCs to vascular smooth muscle cells.<ref name=Niessen2008>{{cite journal|last=Niessen|first=Kyle|coauthors=Aly Karsan|title=Notch Signaling in Cardiac Development|journal=Circulation Research|year=2008|volume=102|pages=1169–1181|doi=10.1161/CIRCRESAHA.108.174318|pmid=18497317}}</ref> Furthermore, Notch is required for the proliferation of cardiomyocytes.<ref name=Niessen2008 /> 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=Niessen2008 /> In humans, mutations in Notch most often result in bicuspid aortic valve disease and calcification of the aortic valve.<ref>{{cite journal|last=Garg|first=V|coauthors=Muth AN, Ransom JF, Schluterman MK, Barnes R, King IN, Grossfeld PD, Srivastava D|title=Mutations in NOTCH1 cause aortic valve disease|journal=Nature|yeardate=September 2005|month=September|volume=437|issue=7056|pages=270–274|url=http://www.nature.com/nature/journal/v437/n7056/full/nature03940.html|accessdate=20 November 2012}}</ref>

=== Bone Morphogenetic Proteins (BMPs) ===

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>{{cite journal|last=Kaartinen|first=V|coauthors=Dudas M, Nagy A, Sridurongrit S, Lu MM, Epstein JA|title=Cardiac outflow tract defects in mice lacking ALK2 in neural crest cells.|journal=Development|yeardate=July 2004|month=July|volume=131|issue=14|pages=3481–90|accessdate=19 November 2012|pmid=15226263|doi=10.1242/dev.01214}}</ref>

=== FGF8 ===

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-Issa2002>{{cite journal|last=Abu-Issa|first=Radwan|coauthors=Smyth, G, Smoak, I, Yamamura, K, & Meyers, EN|title=Fgf8 is required for pharyngeal arch and cardiovascular development in the mouse|journal=Development|yeardate=October 2012|month=October|volume=129|pages=4613–4625|url=http://dev.biologists.org/content/129/19/4613.full.pdf+html|accessdate=November 19, 2012|issue=19}}</ref><ref name=Frank2002>{{cite journal|last=Frank|first=DU|coauthors=Fotheringham, LK, Brewer, JA, Muglia, LJ, Tristani-Firouzi, M, Capecchi, MR, Moon, AM|title=An Fgf8 mouse mutant phenocopies human 22q11 deletion syndrome|journal=Development|yeardate=October 2002|month=October|volume=129|issue=19|pages=4591–603|accessdate=19 November 2012|pmid=12223415|pmc=1876665}}</ref>

=== GATA ===

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===Previous Relevant Research===

Although CNCCs are more prevalent in developing embryos, they have been shown to be retained in adult tissues in a dormant stage called neural crest stem cells.<ref name= "tomita">{{cite journal|last=Tomita|first=Y|coauthors=et al|title=Cardiac neural crest cells contribute to the dormant multipotent stem cell in the mammalian heart|journal=J Cell Biol|yeardate=September 2005|month=September|volume=170|issue=7|pages=1135–1146|accessdate=20 November 2012|pmc=2171522|pmid=16186259|doi=10.1083/jcb.200504061}}</ref> Recent studies have been able to isolate these cardiac neural crest stem cells from mammal hearts and transplant them into the neural crest of a chick embryo.<ref name="tomita" /> These CNCCs were shown to migrate into the developing heart using the same lateral pathway as the embryonic cardiac neural crest cells, and differentiated into neural and glial cells.<ref name="tomita" />

Another study looked at the fate of these CNCCs after a heart attack (myocardial infarction) in young growing mice.<ref name= "tamura">{{cite journal|last=Tamura|first=Y|coauthors=et al|title=Neural crest-derived stem cells migrate and differentiate into cardiomyocytes after myocardial infarction|journal=J Am. Heart Assoc.|yeardate=January 2011|month=January|volume=31|pages=582–589|url=http://atvb.ahajournals.org/content/31/3/582.full.pdf|accessdate=20 November 2012|issue=3}}</ref> The CNCCs in the young mice were tagged with enhanced [[green fluorescent protein]] (EGFP) and then traced.<ref name="tamura" /> Many were concentrated in the outflow tract, and some were found in the ventricular myocardium.<ref name="tamura" /> These cells were also shown to be differentiating into cardiomyocytes as the heart grew.<ref name="tamura" /> Although less were found, these EGFP-labelled CNCCs were still present in the adult heart.<ref name="tamura" /> When a heart attack was induced, the CNCCs aggregated in the ischemic border zone area (BZA, an area of damaged tissue that can still be saved) and helped contribute to the regeneration of the tissue to some extent via differentiation into cardiomyocytes to replace the necrotic tissue.<ref name="tamura" /><ref name= "bza">{{cite journal|last=Axford-Gatley|first=R.A.|coauthors=Wilson, G.J.|title=The "border zone" in myocardial infarction: An ultrastructural study in the dog using an electron-dense blood flow marker|journal=Am. J. Pathol.|yeardate=June 1988|month=June|volume=131|issue=3|pages=452–464|accessdate=20 November 2012|pmc=1880711|pmid=3381878}}</ref>

== References ==