Difference between revisions of "2017 Group Project 3"
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==Developmental Signalling Processes==
==Developmental Signalling Processes==
Heart development is a very complicated and dynamic process that requires a high degree of control and regulation. This control is achieved by
Heart development is a very complicated and dynamic process that requires a high degree of control and regulation. This control is achieved by expressed at different stages of heart development.
Revision as of 11:33, 28 September 2017
|2017 Student Projects|
- 1 Heart
- 1.1 Introduction
- 1.2 Developmental Origin
- 1.3 Developmental Timeline
- 1.3.1 Embryonic Developmental Timeline
- 1.3.2 Historic Developmental Timeline
- 1.4 Developmental Signalling Processes
- 1.5 Current Research And Findings
- 1.6 Animal Models
- 1.7 Abnormal Development
- 1.8 Future Questions
- 1.9 Glossary of Terms
- 1.10 References
- This is very early stage of content development. Of all the possible topics this is definitely the MOST researched topic to date. You have this week to make significant progress on this page.
- Where is the timeline of development.
- Where is the timeline of key discoveries
- Splanchnic mesoderm and neural crest contribution
- Differentiation of different cardiac cell types
- Cardiac conduction system development
- Cardiomyocyte differentiation/function
- Cardiac stem cells
The cardiovascular system is the first system to develop and function in the human embryo. The rapid cardiac development is essential as the growing embryo can no longer receive oxygen and essential nutrients via diffusion alone, hence a circulatory system and a contractile heart mechanism is required to supply the embryo. We recognise the hearts normal development is vital for foetal life, and hence we have chosen to document the development of the heart from gastrulation to birth. Any defects occurring during the developmental processes can lead to congenital heart abnormalities. However, early cardiac development is a multifaceted procedure and is associated with other developmental processes such as: embryonic folding, coelom formation, and vascular development .
Through researching the advances in technology, coupled with the biological use of suitable animal models  our understanding of embryological cardiac development has evolved, and we are piecing together the mechanism underlying this development. This page will outline the importance of how heart abnormalities arise, the treatments available and the possible treatments to be developed in the future. Due to the major knowledge gaps in current embryological heart research, we acknowledge that this will impact our assignment, and aim to address further research concepts that will improve our understanding.
In the developing embryo the lateral plate mesoderm splits into somatic and splanchnic layers, the latter is comprised of cardiac progenitor cells . The somatic mesoderm lines the ectoderm, the splanchnic mesoderm lines the endoderm, and in between lies an embryonic coelom  . At the end of week three, the heart develops from splanchnic mesoderm of the cardiogenic region of the embryonic plate. At the cranial end of the embryo, anterior to the developing neural tube is the initial origin of heart formation.
Originally, as seen in figure 2 the cardiogenic region forms laterally of the paraxial mesoderm and primitive streak of the embryonic disc. Due to the natural mesenchymal cell organisation of the mesoderm, cells ‘migrate’ and fuse at the midline of the cranial end of the embryo forming the cardiac crescent just prior cardiac tube formation and folding. As in figure 2, endoderm surrounding the primitive gut contracts, and brings the cardiogenic precursor regions of the splanchnic region towards the midline. At this time, early heart formation occurs in the form of angioblastic cords of the splanchnic mesoderm. The angioblastic cords develop into separate endochondral heart tubes moving closer together as the foregut pinches together and the yolk sac contracts into the embryo. Fusion of the two heart tubes is facilitated by apoptosis  . The origin of the primitive heart is in the early pericardial coelom, which is later developed into the pericardial cavity, through fusion of the pleuropericardial folds to separate the pleural cavities at the later development of the lungs (see figure 4) .
Embryonic Developmental Timeline
Primary Heart Field and Heart Tube Formation
Secondary Heart Field and Cardiac Looping
Cardiac Neural crest and Outflow tract
Atrial and Ventricular Septation
Proepicardium and Coronary Heart Development
MAIN ARTICLE --> http://www.springer.com/cda/content/document/cda_downloaddocument/9781588294432-c2.pdf?SGWID=0-0-45-387660-p173728389 http://www.nature.com/pr/journal/v57/n2/full/pr200525a.html?foxtrotcallback=true
Historic Developmental Timeline
Developmental Signalling Processes
Heart development is a very complicated and dynamic process that requires a high degree of control and regulation. This control is achieved by several temporally regulated signalling cascade (Fig. 1) expressed at different stages of heart development.
According to the primary mode of action, Wnt signalling pathways have been divided into two major classes, canonical and non-canonical Wnt signalling pathways. Both the pathways have a role in different stages of cardiac development which could be overlapping or independent of each other. The canonical Wnt signalling pathway involves β-catenin and is activated by a number of ligands such as Wnt-1, Wnt-2, Wnt-3A, Wnt-8A, Wnt-8B, Wnt-8C, Wnt-10A, and Wnt-10B. However, the non-canonical signalling pathway is associated with planar cell polarity and Wnt/Ca2+ pathways that are activated by different ligands such as Wnt4, Wnt5A, Wnt5B, Wnt6, Wnt7A, Wnt7B, and Wnt11 .
Canonical/β -catenin signaling is essential for mesoderm formation. Upon binding of the Wnt ligands to the Frizzled receptor, a seven-transmembrane receptor, or the co-receptor LRP-5/6, the Canonical signaling pathway is activated. This leads to cytoplasmic accumulation of β -catenin in one side of the embryo and its translocation to the nucleus where it drives the activation of transcription factors required to determine the site at which mesoderm and endoderm formation will occur in the embryo. Animal studies have shown that the lack of nuclear accumulation of β -catenin results in inability of axis formation and mesoderm development whereas overexpression of β -catenin leads to the formation of secondary axis and ectopic expression of mesoderm signals. Also, homozygous deletion of β -catenin in mouse models results in absence of primitive streak and mesoderm formation .
Once mesoderm formation proceeds, the β -catenin signal must be shut down by inhibiting factors otherwise cardiac mesoderm formation will be stopped. This indicates that canonical signaling act as a switch that either induces or suppresses cardiac development. One of the inhibiting factors include dickkopf-1(DKK1) which is an extracellular Wnt inhibitor promotes the expression of cardiac-inducing factor in the endoderm such as Hex. The latter activates paracrine factors to direct adjoining cells towards cardiac fate .
The Notch pathway
Current Research And Findings
Ventricular Septal Defect
 - ventricular septal defect (Penny and Vick)
Atrial Septal Defect
 - atrial septal defects (Giva, Martins & Wald)
Atrioventricular Septal Defect
Glossary of Terms