Detailed Cardiac - Sinus Node: Difference between revisions

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T-Box 3 (Tbx3) gene located at 12q24.2, the 723 amino acid protein acts as a homeobox transcription factor. Tbx3 expression represses the transcriptional program of atrium chamber myocardium for  
T-Box 3 (Tbx3) gene located at 12q24.2, the 723 amino acid protein acts as a homeobox transcription factor. Tbx3 expression represses the transcriptional program of atrium chamber myocardium for  


:'''Links:'''  [[Developmental Signals - Tbx|Tbx]] | [https://www.omim.org/entry/601621  OMIM TBX3]


===Tbx18===
T-Box 18 (Tbx18) gene located at 6q14.3 appears to be a key in sinoatrial node development.
:'''Links:'''  [[Developmental Signals - Tbx|Tbx]] | [https://www.omim.org/entry/604613  OMIM TBX18]


:'''Links:'''  [[Developmental Signals - Tbx|Tbx]] | [https://www.omim.org/entry/601621  OMIM TBX3]
===Hcn4===
===Hcn4===


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===Shox2===
===Shox2===
Short Stature Homeobox 2 (SHOX2) gene located at 3q25.32, the protein acts as a homeobox transcription factor. Shox2 represses Nx2.5 and activates expression of the transcription factor islet 1 (Isl1).
Short Stature Homeobox 2 (SHOX2) gene located at 3q25.32, the protein acts as a homeobox transcription factor. Shox2 represses Nx2.5 and activates expression of the transcription factor islet 1 (Isl1).


* mouse og12 gene - developmental sinus venosus (aorta), female genitalia, diencephalon, mesencephalon and myelencephalon, nasal capsula, palate, eyelid, and limbs
* mouse og12 gene - developmental sinus venosus (aorta), female genitalia, diencephalon, mesencephalon and myelencephalon, nasal capsula, palate, eyelid, and limbs

Latest revision as of 13:02, 19 February 2017

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This content was contributed by Prof Robert H. Anderson.


Anderson RH. Teratogenecity in the setting of cardiac development and maldevelopment. (2016)

Please note that the content is still at the early draft stage and will be the basis of updating the online cardiac development information with a more detailed description as shown by the page links below (shown in red if not yet existing).

Detailed Cardiac: Systemic Venous Sinus | Pulmonary Vein | Superior Interatrial Fold | Atrioventricular Cushions | Atrioventricular Canal | Interventricular Communication | Subpulmonary Infundibulum | Arterial Roots | Intrapericardial Arterial Trunks | Extrapericardial Arterial Channels | Sinus Node | Atrioventricular Conduction Axis


Cardiovascular Links: cardiovascular | Heart Tutorial | Lecture - Early Vascular | Lecture - Heart | Movies | 2016 Cardiac Review | heart | coronary circulation | heart valve | heart rate | Circulation | blood | blood vessel | blood vessel histology | heart histology | Lymphatic | ductus venosus | spleen | Stage 22 | cardiovascular abnormalities | OMIM | 2012 ECHO Meeting | Category:Cardiovascular
Historic Embryology - Cardiovascular 
1902 Vena cava inferior | 1905 Brain Blood Vessels | 1909 Cervical Veins | 1909 Dorsal aorta and umbilical veins | 1912 Heart | 1912 Human Heart | 1914 Earliest Blood-Vessels | 1915 Congenital Cardiac Disease | 1915 Dura Venous Sinuses | 1916 Blood cell origin | 1916 Pars Membranacea Septi | 1919 Lower Limb Arteries | 1921 Human Brain Vascular | 1921 Spleen | 1922 Aortic-Arch System | 1922 Pig Forelimb Arteries | 1922 Chicken Pulmonary | 1923 Head Subcutaneous Plexus | 1923 Ductus Venosus | 1925 Venous Development | 1927 Stage 11 Heart | 1928 Heart Blood Flow | 1935 Aorta | 1935 Venous valves | 1938 Pars Membranacea Septi | 1938 Foramen Ovale | 1939 Atrio-Ventricular Valves | 1940 Vena cava inferior | 1940 Early Hematopoiesis | 1941 Blood Formation | 1942 Truncus and Conus Partitioning | Ziegler Heart Models | 1951 Heart Movie | 1954 Week 9 Heart | 1957 Cranial venous system | 1959 Brain Arterial Anastomoses | Historic Embryology Papers | 2012 ECHO Meeting | 2016 Cardiac Review | Historic Disclaimer


Search: PubMed - Anderson RH

Detailed Cardiac: Systemic Venous Sinus | Pulmonary Vein | Superior Interatrial Fold | Atrioventricular Cushions | Atrioventricular Canal | Interventricular Communication | Subpulmonary Infundibulum | Arterial Roots | Intrapericardial Arterial Trunks | Extrapericardial Arterial Channels | Sinus Node | Atrioventricular Conduction Axis

Appearance and Remodelling of the Sinus Node

Introduction

Cardiac Conduction System
Cardiac Conduction System

The sinoatrial node (SAN) is the primary pacemaker of the heart that initially develops from part of pro-pacemaking embryonic venous pole that expresses both Hcn4 and the transcriptional factor Shox2.[1] The chicken embryo has been used as a model of SAN development, where early canonical Wnts expression within the right lateral plate mesoderm just posterior of the heart field results in development of these cells.[2]


The adult node is a mixture of about 10,000 cells distinct cardiomyocytes located at the entry of the right superior caval vein (SVC) into the right atrium.


Cardiovascular Links: cardiovascular | Heart Tutorial | Lecture - Early Vascular | Lecture - Heart | Movies | 2016 Cardiac Review | heart | coronary circulation | heart valve | heart rate | Circulation | blood | blood vessel | blood vessel histology | heart histology | Lymphatic | ductus venosus | spleen | Stage 22 | cardiovascular abnormalities | OMIM | 2012 ECHO Meeting | Category:Cardiovascular
Historic Embryology - Cardiovascular 
1902 Vena cava inferior | 1905 Brain Blood Vessels | 1909 Cervical Veins | 1909 Dorsal aorta and umbilical veins | 1912 Heart | 1912 Human Heart | 1914 Earliest Blood-Vessels | 1915 Congenital Cardiac Disease | 1915 Dura Venous Sinuses | 1916 Blood cell origin | 1916 Pars Membranacea Septi | 1919 Lower Limb Arteries | 1921 Human Brain Vascular | 1921 Spleen | 1922 Aortic-Arch System | 1922 Pig Forelimb Arteries | 1922 Chicken Pulmonary | 1923 Head Subcutaneous Plexus | 1923 Ductus Venosus | 1925 Venous Development | 1927 Stage 11 Heart | 1928 Heart Blood Flow | 1935 Aorta | 1935 Venous valves | 1938 Pars Membranacea Septi | 1938 Foramen Ovale | 1939 Atrio-Ventricular Valves | 1940 Vena cava inferior | 1940 Early Hematopoiesis | 1941 Blood Formation | 1942 Truncus and Conus Partitioning | Ziegler Heart Models | 1951 Heart Movie | 1954 Week 9 Heart | 1957 Cranial venous system | 1959 Brain Arterial Anastomoses | Historic Embryology Papers | 2012 ECHO Meeting | 2016 Cardiac Review | Historic Disclaimer

Some Recent Findings

  • Computational analysis of the human sinus node action potential: model development and effects of mutations[3] "The sinoatrial node (SAN) is the normal pacemaker of the mammalian heart. Over several decades, a large amount of data on the ionic mechanisms underlying the spontaneous electrical activity of SAN pacemaker cells has been obtained, mostly in experiments on single cells isolated from rabbit SAN. This wealth of data has allowed the development of mathematical models of the electrical activity of rabbit SAN pacemaker cells. Our aim was to construct a more comprehensive model of the electrical activity of a human SAN pacemaker cell, using recently obtained electrophysiological data from human SAN pacemaker cells. We based our model on the recent Severi-DiFrancesco model of a rabbit SAN pacemaker cell. The action potential and calcium transient of the resulting model are close to the experimentally recorded values: the model has a much smaller 'funny current' (If ) than do rabbit cells, but its modulatory role is highly similar. Changes in pacing rate upon the implementation of mutations associated with sinus node dysfunction agree with the clinical observations. This agreement holds for both loss-of-function and gain-of-function mutations in the HCN4, SCN5A, and KCNQ1 genes, underlying ion channelopathies in If , fast sodium current, and slow delayed rectifier potassium current, respectively. We conclude that our human SAN cell model can be a useful tool in the design of experiments and the development of drugs that aim to modulate heart rate.
  • Development of the cardiac pacemaker[4] "The sinoatrial node (SAN) is the dominant pacemaker of the heart. Abnormalities in SAN formation and function can cause sinus arrhythmia, including sick sinus syndrome and sudden death. A better understanding of genes and signaling pathways that regulate SAN development and function is essential to develop more effective treatment to sinus arrhythmia, including biological pacemakers. In this review, we briefly summarize the key processes of SAN morphogenesis during development, and focus on the transcriptional network that drives SAN development."
More recent papers  
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Search term: Sinus Node Development

<pubmed limit=5>Sinus Node Development</pubmed>

Molecular

Wnt

A secreted glycoprotein patterning switch with different roles in different tissues and signaling has generally been divided into the canonical and non-canonical pathways. The name was derived from two drosophila phenotypes wingless and int and the gene was first defined as a protooncogene, int1.

Canonical Pathway

  1. Wnt binds the surface receptor Frizzled (Fz) and LRP5/6 receptor complex
  2. Induces the stabilization of beta-catenin (through the DIX and PDZ domains of Dishevelled and other factors including Axin, glycogen synthase kinase 3 and casein kinase 1)
  3. Beta-catenin translocates into the nucleus
  4. Beta-catenin complexes with members of the LEF/TCF family of transcription factors.
  5. Transcriptional induction of target genes.
  6. Beta-catenin is then exported from the nucleus and degraded via the proteosomal machinery.


Links: Wnt | Wnt Canonical Pathway

Tbx3

T-Box 3 (Tbx3) gene located at 12q24.2, the 723 amino acid protein acts as a homeobox transcription factor. Tbx3 expression represses the transcriptional program of atrium chamber myocardium for

Links: Tbx | OMIM TBX3

Tbx18

T-Box 18 (Tbx18) gene located at 6q14.3 appears to be a key in sinoatrial node development.

Links: Tbx | OMIM TBX18

Hcn4

Hyperpolarization-Activated Cyclic Nucleotide-Gated Potassium Channel 4 (HCN4) gene located at 15q24.1, the 1,203 amino acid protein contains 6 putative transmembrane segments, a pore region, and a cyclic nucleotide-binding domain.

Links: [OMIM HCN4

Shox2

Short Stature Homeobox 2 (SHOX2) gene located at 3q25.32, the protein acts as a homeobox transcription factor. Shox2 represses Nx2.5 and activates expression of the transcription factor islet 1 (Isl1).

  • mouse og12 gene - developmental sinus venosus (aorta), female genitalia, diencephalon, mesencephalon and myelencephalon, nasal capsula, palate, eyelid, and limbs


Links: OMIM SHOX2

ISL1

ISL Lim Homeobox 1 (ISL1) gene located at 5q11.1 is a member of the LIM/homeodomain family of transcription factors that binds to the enhancer region of the insulin gene. Functions in survival, proliferation, and function of pacemaker cells throughout development.[5]


Links: OMIM ISL1

Abnormalities

Sinus node dysfunction (SND) or sick sinus syndrome (SSS) can occur in the elderly.

References

  1. <pubmed>26682210</pubmed>
  2. <pubmed>23519212</pubmed>
  3. <pubmed>28185290</pubmed>
  4. <pubmed>27770149</pubmed>
  5. <pubmed>26193633</pubmed>

Reviews

<pubmed>26023305</pubmed> <pubmed>24672485</pubmed> <pubmed></pubmed> <pubmed></pubmed>

Articles

<pubmed>27291063</pubmed> <pubmed>26682210</pubmed> <pubmed>26611337</pubmed> <pubmed>26835096</pubmed>

Terms

Heart

  • angioblastic cords - Groups or ‘columns’ of embryonic precursor cells which will form the walls of both arteries and veins.
  • apex - Anatomical term referring to the most inferior, left, downwards pointing part of the heart.
  • aorta - The largest artery in the human body originating in the left ventricle. The aorta ascends, arches over the heart and then descends through the abdomen.
  • aortic arch arteries - (pharyngeal arch arteries) Each early developing pharyngeal arch contains a lateral pair of arteries arising from the aortic sac, above the heart, and running into the dorsal aorta. Later in development these arch arteries are extensively remodelled to form specific components of the vascular system.
  • aortic valve - Three-leaflet valve located at the junction between the left ventricle and aortic entrance.
  • aortic vestibule - Smooth-walled portion of the left ventricle directly below the aortic valve.
  • aorticopulmonary septum - Division between the aorta and the pulmonary trunk formed from the bulbar ridges.
  • atresia - Abnormal closure or absence of a body vessel or orifice.
  • atrioventricular canal - Junction between the primitive atrium and primitive ventricle in the embryo. This canal splits to later form two atrioventricular canals which consequently form the valves of the adult heart.
  • bulbar ridges - Endocardial cushion tissue located in the bulbus cordis extending into the truncus arteriosus thus forming ridges. These fuse together to form the aorticopulmonary septum.
  • bulbus cordis - A region of the early developing heart tube forming the common outflow tract, will differentiate to form three regions of the heart.
  • cardiac jelly - Term used in early heart development to describe the initial gelatinous or sponge-like connective tissue separating the myocardium and heart tube endothelium.
  • cardiogenic region - The area in the embryo where the precursor cells for heart development lie.
  • chordae tendineae - Cord-like tendons connecting the papillary muscles to the leaflets of the mitral and tricuspid valves.
  • congenital heart disease - Abnormal structure or function of the heart due to a developmental defect arising prior to birth.
  • connective tissue - Fibrous tissue that acts to support body structures or bind other forms of tissue.
  • conus arteriosus - An embryological heart outflow structure, that forms in early cardiac development and will later divides into the pulmonary artery and aorta. Term is also used clinically to describe the malformation of the cardiac outflow pattern, where only one artery arises from the heart and forms the aorta and pulmonary artery.
  • coronary sinus - a venous sinus emptying into the right atrium that collects blood from the myocardium of the heart. The coronary sinus is the largest cardiac vein.
  • cyanosis - Blue colouration of the skin and mucous membrane due to poor oxygenation of the blood.
  • dorsal aortae - Two largest arteries either side of the midline which later fuse to form the descending portion of the aorta.
  • dorsal mesocardium - The mesentery attaching the heart to the dorsal wall of the pericardial coelom. This breaks down to form a space known as the transverse pericardial sinus.
  • dyspnoea - Shortness of breath.
  • endocardial cushions - Swellings of migrated cells on the inner lining of the heart located in the atrioventricular canal.
  • endocardial heart tubes - Two tubes formed from the cardiogenic plate in the developing embryo. These form the primordium of the truncus arteriosus, the atrium and the ventricles; later invested with myocardium.
  • endocardium - The epithelial membrane lining the inside surface of heart, which along with the endothelial layer forms a continuous lining of the entire cardiovascular system. The endocardium, like the majority of the heart is mesoderm in origin.
  • endothelium - A simple squamous epithelium lining blood vessels.
  • epicardium - The outer layer of heart tissue.
  • fibrous trigone - (trigonum fibrosum) term describing the dense connective tissue between the aortic ring and the atrioventricular ring and has a left and right component. The right fibrous trigone (trigonum fibrosum dextrum) lies between the aortic ring and the right atrioventricular ring. The left fibrous trigone (trigonum fibrosum sinistrum) lies between the aortic ring and the left atrioventricular ring.
  • foramen ovale - Shunt allowing blood to enter the left atrium from the right atrium. It is located in the septum secundum.
  • foramen primum - Original space between the septum primum and the fused endocardial cushions as the septum primum grows towards the cushions.
  • foramen secundum - Refers to the coalesced perforations in the septum primum after it has fused with the endocardial cushions.
  • fossa ovalis - (oval fossa, annulus ovalis) Region in the postnatal atrial septum where the foramen ovale was located during embryonic development. Appears as an indentation in the right atrium septum.
  • heart murmur - Extra heart sounds appearing upon auscultation due to turbulent blood flow.
  • hypertrophy - Increase in size of an organ or tissue due to enlargement of component cells.
  • inferior vena cava - (IVC) Large vein which carries deoxygenated blood from the lower half of the body to the right atrium.
  • inflow tract - Entrance of blood into the heart tube; the sinus venosus portion of the tube.
  • infundibulum - Smooth-walled portion of the right ventricle directly below the pulmonary valve.
  • interventricular septum - Wall of muscular tissue growing from the base of the heart dividing the primitive ventricle into the left and right ventricles.
  • interventricular foramen - Space between the interventricular septum and the fused endocardial cushions. The foramen closes when the septum fuses with the endocardial cushions and bulbar ridges.
  • intraembryonic coelom - Initial embryonic space in lateral plate mesoderm that will be separated to form the three major body cavities: pericardial, pleural and peritoneal cavity. The lateral plate mesoderm is divided by this space into splanchnic and somatic mesoderm.
  • left horn of sinus venosus - The left side of the sinus venosus (initially symmetrical with the right) collecting blood from half of the paired veins: common cardinal veins, umbilical veins and vitelline veins. Later the left horn diminishes and becomes the small coronary sinus.
  • mitral valve - (Bicuspid valve) two leaflet valve located on the left side of the heart, that is between the left atrium and ventricle.
  • myocardium - The middle layer of the heart wall composed of cardiac muscle.
  • neural crest mesenchyme - Connective tissue arising from critical cells in the cranial region of the embryo. These paired dorsal lateral streaks of cells migrate throughout the embryo and can differentiate into many different cell types (= pluripotential). Those that remain on the dorsal neural tube form the sensory spinal ganglia (DRG), those that migrate ventrally form the sympatheitic ganglia. Neural crest cells also migrate into the somites and regions through the entire embryo.
  • outflow tract - Exit of blood from the heart tube formed by the truncus arterioles.
  • oval fossa - (fossa ovalis, annulus ovalis) Region in the postnatal atrial septum where the foramen ovale was located during development. Appears as an indentation in the right atrium septum.
  • papillary muscles - Small muscles found on the inner myocardium of the left and right ventricles. They are attached to the mitral and tricuspid valves via the chordae tendineae and serve to limit the movements of the valves.
  • patent foramen ovale - Abnormality in atrial septum due to failure of the atrial septum to close at the foramen ovale. (More? Atrial Septal Defects)
  • pericardial coelom - (pericardial cavity) The anatomical body cavity in which the heart lies. The pericardial cavity forms in the lateral plate mesoderm above the buccopharyngeal membrane, as part of the early intraembryonic coelom. This cavity is initially continuous with the two early pleural cavities. Note the single intraembryonic coelom forms all three major body cavities: pericardial cavity, pleural cavity, peritoneal cavity.
  • primordial atrium - Common cavity in the upper portion of the developing heart. Later divides to form the left and right atria.
  • primordial ventricle - Common cavity in the lower portion of the developing heart. Later divides to form the left and right ventricles.
  • pulmonary circulation - Carries blood between the heart and lungs.
  • pulmonary trunk - A vessel that arises from the right ventricle of the heart, extends upward, and divides into the right and left pulmonary arteries that transport deoxygenated blood to the lungs.
  • pulmonary valve - Three-leaflet valve located at the junction between the right ventricle and the pulmonary trunk.
  • pulmonary veins - Four veins that allow oxygenated blood from the lungs to empty into the left atrium.
  • right horn of sinus venosus - The right side of the sinus venosus (initially symmetrical with the left) collecting blood from half of the paired veins: common cardinal veins, umbilical veins and vitelline veins. Later the right horn dilates, receiving all the veins, and becomes the sinus venarum of the right atrium.
  • second heart field - (SHF) splanchnic mesoderm that forms progenitors important for heart formation.
  • semilunar valves - Flaps of endocardium and connective tissue reinforced by fibres which prevent the valves from turning inside out. They are shaped like a half moon, hence the name semilunar. The semilunar valves are located between the aorta and the left ventricle and between the pulmonary artery and the right ventricle.
  • septum primum - Original structure growing from the roof of the heart towards the endocardial cushions dividing the primitive atrium.
  • septum secundum - Second structure growing to the right of the septum primum dividing the primitive atrium.
  • sinoatrial node - Specialised cardiomyocyte pacemaking region of the heart located at the entry of the right superior caval vein (SVC) into the right atrium. (More? Detailed Cardiac - Sinus Node)
  • sinus venosus - (systemic venous sinus) An early developmental cardiovascular structure, thin walled cavity, forming the input to developing heart which has 3 venous inputs (vitelline vein, umbilical vein, common cardinal vein). Later in heart development this structure gets incorporated into the wall of the future right atrium. (More? Systemic Venous Sinus)
  • sinuatrial orifice - The opening between the sinus venosus and right atrium which has two valve leaflets to prevent backflow of blood.
  • sinus venarum - Smooth-walled portion of the adult right atrium; originally the left horn of the sinus venous.
  • splanchnic mesoderm - Gastrointestinal tract (endoderm) associated mesoderm formed by the separation of the lateral plate mesoderm into two separate components by a cavity, the intraembryonic coelom. Splanchnic mesoderm is the embryonic origin of the second heart field, gastrointestinal tract connective tissue, smooth muscle, blood vessels and contribute to organ development (heart, pancreas, spleen, liver).
  • stenosis - Abnormal narrowing of a blood vessel or orifice.
  • superior vena cava - (SVC) Short vein which carries deoxygenated blood from the upper half of the body to the right atrium.
  • systemic circulation - Carries oxygenated blood away from the heart to the other body organs and returns to the heart deoxygenated.
  • tachypnoea - Abnormally rapid breathing rate.
  • trabeculae - (trabeculations)Muscular beams located within the ventricles and parts of the atria of the heart.
  • transverse pericardial sinus - Dorsal area within the pericardial coelom, initially occupied by the dorsal mesocardium.
  • tricuspid valve - Three leaflet valve located in the right atrioventricular canal i.e. between the right atrium and ventricle.
  • tricuspid atresia - Abnormality of the tricuspid valve between the right atrium and right ventricle.
  • truncus arteriosus - An embryological heart outflow structure, that forms in early cardiac development and will later divides into the pulmonary artery and aorta. Term is also used clinically to describe the malformation of the cardiac outflow pattern, where only one artery arises from the heart and forms the aorta and pulmonary artery.
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Cite this page: Hill, M.A. (2024, March 28) Embryology Detailed Cardiac - Sinus Node. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Detailed_Cardiac_-_Sinus_Node

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