Cardiac neural crest
This complex refers to the cells found amongst the midotic placode and somite 3 destined to undergo epithelial-mesenchymal transformation and migration to the heart via pharyngeal arches 3, 4 and 6.
[2] The cardiac neural crest complex plays a vital role in forming connective tissues that aid in outflow septation and modelling of the aortic arch arteries during early development.
[3] Consequently, the removal of cardiac crest cells that populate in pharyngeal arches has flow on effects on the thymus, parathyroid and thyroid gland.
[5][6][7] They extend from the otic placodes (the structure in developing embryos that will later form the ears) to the third somites (clusters of mesoderm that will become skeletal muscle, vertebrae and dermis).
Molecules such as Wnt, fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) provide signals which induce the progenitor cells to become CNCCs.
[2] From here, a subpopulation of cells will develop into the endothelium of the aortic arch arteries while others will migrate into the outflow tract to form the aorticopulmonary and truncal septa.
[11] Prior to migration, during a process known as epithelial-mesenchymal transition (EMT), there is a loss of cell contact, remodelling of the cytoskeleton and increased motility and interaction with extracellular components in the matrix.
This suppression mechanism occurs via the growth factor BMP signalling to turn on a transcriptional repressor Smad-interacting protein 1 (Sip1) and marks the beginning of the epithelial-mesenchymal transition.
[1] Impaired Cx43 function in transgenic mice leads to altered coronary artery patterns and abnormal outflow tracts.
[16] Appropriate outflow tract formation relies on a morphogen concentration gradient set up by fibroblast growth factor (FGF) secreting cells.
[2] The enzyme arginyltransferase creates this environment by adding an arginyl group onto newly synthesised proteins during post-translational modification.
[19] This process aids cells motility and ensures the proteins contained within the actin cytoskeleton is prepped for migration.
[2] Little is known about this pausing mechanism, but studies conducted in chicks have uncovered the role of mesoderm expressed factors EphrinB3 and EphrinB4 in forming fibronectin attachments.
Cells leading this migration maintain contact with the extracellular matrix and contain filopodia which act as extensions towards the ectodermal pharyngeal arches.
Migrating cardiac neural crest cells will populate at the correct pharyngeal arches under signalling guidance from EphrinA and Ephrin B variations.
[21] Normally, early development of the outflow tract begins with a single vessel that forms bilateral symmetrical branches at the aortic sac within pharyngeal arches.
This process requires the elongation of the outflow tract as a prerequisite to ensure the correct series of looping and cardiac alignment.
[9] The malformation of the heart and its associated great vessels depends on the extent and location of the cardiac neural crest complex ablation.
[9] Complete removal of cardiac neural crests results in persistent truncus arteriosus characterised in most cases by the presence of just one outflow valve and a ventricular septal defect.
[22] Mesencephalic neural crest cells interfere with normal development of cardiac outflow septation as its presence leads to persistent truncus arteriosus.
[9] Other outcomes of cardiac outflow anomalies includes Tetralogy of Fallot, Eisenmenger's complex, transposition of the great vessels and double outlet right ventricle.
[9] Overriding aorta is caused by the abnormal looping during early development of the heart and is accompanied with ventricular septal defects.
[24] Due to its population in pharyngeal arches, removal of the cardiac neural crest complex has flow on effects on the thymus, parathyroid and thyroid gland.
[11] Into the pharyngeal arches and Truncus arteriosus (embryology), forming the aorticopulmonary septum[25] and the smooth muscle of great arteries.
[26] The CNCCs interact with the cardiogenic mesoderm cells of the primary and secondary heart fields, which are derived from the cardiac crescent and will give rise to the endocardium, myocardium, and epicardium.
[27] For example, CNCCs are required for the formation of the aorticopulmonary septum (APS) that directs cardiac outflow into two tracts: the pulmonary trunk and the aorta of the developing heart.
These anomalies include persistent truncus arteriosus (PTA), double outlet right ventricle (DORV), tetralogy of Fallot and DiGeorge syndrome.
[29] 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.
There are emergency treatments that hospitals can administer, such as angioplasty or surgery, but after that patients will likely be on medication for the long term and are more susceptible to heart attacks in the future.
