2018 Group Project 4

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Projects 2018: 1 Adrenal Medulla | 3 Melanocytes | 4 Cardiac | 5 Dorsal Root Ganglion

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Neural Crest and Cardiac Development

Introduction of the heart

The heart is a muscular organ which plays a critical role in the circulatory system by mechanically pumping blood to various organs around the body for the exchange of nutrients and gases. It is located at the center of the chest, right behind the sternum and is tilted slightly to the left. The heart has four different chambers which are compartmentalized by semilunar and atrioventricular valves into the left and right atria and ventricles

Cardiac neural crest cells

Neural crest cells are a population of multipotent cells which arises during embryonic development at the dorsal neural tube. These cells are capable of migrating and differentiating throughout the body to give rise to many different cell types. The cardiac neural crest cells (CNCCs) are a subpopulation of the cranial neural crest cells and migrate ventrally from the dorsal neural tube and accumulate in the circumpharyngeal ridge. PubmedParser error: Invalid PMID, please check. (PMID: [1]) The cardiac neural crest wells will then proceed into the pharyngeal arches as each arch develops.

CNCCs are not critical in the initial formation of vessels but they are needed for the remodelling of subsequent arteries, and will give rise to the smooth muscle tunics of the great arteries.PubmedParser error: Invalid PMID, please check. (PMID: [2])

History of cardiac neural crest cells

CNCC was first discovered in a study carried out on chicks by Kirby et al., (1983), where it was discovered that by ablating a region of neural crest cells, embryos lacked aorticopulmonary septation. The subregion of cranial neural crest ablated by Dr. Kirby is now known as the “cardiac neural crest”, not because the cells of this region are dedicated to migrating to the heart, but rather for their importance in crest-derived ectomesenchyme of cardiovascular development. [1]

Structure of the Cardiovascular Network/Histology/Anatomy/Physiology

Anatomy of the Heart Diagram.jpg Structure of the Adult Human Heart

Copyright

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The is heart is considered the hardest working organ in the body. Without the heart functioning the human body would cease to function and carry out everyday tasks. The heart consists of four chambers separated by the septum containing, two atria (right atrium, left atrium), two ventricles (left & right). The right side of the heart contains deoxygenated blood and the left side of the heart contains oxygenated blood. The right atrium collects blood returning from the body (Deoxygenated), the left atrium collects blood (oxygenated) returning from the lungs. The right ventricle pumps blood to the lungs and the left ventricle propels blood into the aorta where blood is dispersed to the rest of the body for consumption. There are four valves located in the heart that prevent the backflow of blood. An average heart rate is anywhere between 60-100 beats per minute. For babies, it can be higher around 120-140 beats per minute, for well-conditioned athletes their heart rates can be below 40 beats per minute.

Directional flow of blood through the Heart and its chambers (Red= Oxygenated, Blue=Deoxygenated)

Inferior and superior vena cava--->Right Atrium--->through Tricuspid valve--->Right Ventricle--->Pulmonary Semi-Lunar Valve--->Pulmonary Trunk--->left & Right Pulmonary arteries---> Left & Right Pulmonary Veins---> Left Atrium---> Bicuspid Valve---> Left Ventricle---> Aortic Semilunar Valve---> Trunk of the Aorta---> Aortic Arteries---> Descending Aorta. Then after the blood has traveled through the body and the oxygen has been consumed by the bodies tissues, the blood returns to the heart via veins and the inferior vena cava and superior vena cava. The process repeats.

Histology

Histology of the Heart.gif

Cardiovascular System

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Cardiovascular System.jpg

Embryonic Origins/Embryonic Contributions

~~ Cardiac neural crest cells can become: - melanocytes near the heart region - neurons associated with the heart - cartilage - connective tissue → they form the connective tissue wall of the large arteries from the heart, as well as the septum between the branches in the heart.

The heart mainly forms from the mesoderm, however cardiac neural crest cells play a crucial part in the development of the heart. CNCC are mixed in to the heart as the heart is forming. They form the septum and the arteries coming from the heart.

Early Development

Development of the heart in the fetus and partitioning of the heart into four chambers

Later Development

Developmental time course/carnegie stages/overview

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cardiac neural crest migrates through the aortic arches and enters the outflow tract of the heart = week 5-6, day 32-37. Outflow tract and ventricular septation complete = week 9, day 57+ |}

Cell signalling involved/Molecular Mechanisms/Factors/Genes

~~ z5229189 Cardiac Crest Cell Migration

  1. Induction of CarNCCs and EMT

Cardiac neural crest cells undergo EMT. Snail2 inhibits expression of cadherins RhoA/B remodel the cytoskeleton of the cells for ready migration

  1. Initial migration of cardiac neural crest cells

CNCC express integrin and MMP-2 to break down ECM to go to the circumpharyngeal ridge

  1. Pause in circumpharyngeal ridge

Cardiac neural crest cells stop migrating and briefly populate the circumpharyngeal ridge The pharyngeal arches are still developing and must regress before migration can continue

  1. Migration into the pharyngeal arches and condensation around the arch arteries

Cardiac neural crest cells express different factors that target the cells to the pharyngeal arches Slit cells can target cells to migrate to arch 3. FGF-8 targets for arch 4. EphA targets for arch 6. Rac1 and Sdf1 are both expressed in the cells, causing them to condensate around the arch arteries.

  1. Migration into the cardiac outflow tract and condensation

Semaphorin is expressed and causes the cells to migrate further to the cardiac outflow tract Notch and BMP are then expressed condensing the cells, forming the semilunar valve and aoticopulmonary septum.

→ Cardiac Development, Kirby M., 2010

Human Congenital Heart Diseases

Current research/main animal models/future questions

Glossary

References

  1. Kirby ML & Stewart DE. (1983). Neural crest origin of cardiac ganglion cells in the chick embryo: identification and extirpation. Dev. Biol. , 97, 433-43. PMID: 6852374