The Heart

Prepared by: NGO, Ricky Justin N.

Heart
• an organ that pumps blood throughout
the body via the circulatory system,
supplying oxygen and nutrients to the
tissues and removing carbon dioxide and
other wastes
Heart

• Very important in human embryology due to heart diseases

• An active area of research

• The hearts of different vertebrates originate in a similar way

 Fish
• Singular muscular tube
• Divided into:
• Sinus venosus
• Atrium
• Ventricle
• Outflow tract
 Fish Heart
• Single circulation
 Amphibia
• Separate pulmonary and
systemic circulation
• Atria divided into:
• Left atrium
• Right atrium
• Single ventricle – separate
blood flow
 Birds and Mammals
• Complete double circulation
• Right atrium – receives blood
from organs
• Right ventricle – sends blood
to the lungs
• Left atrium – receives blood
from the lungs
• Left ventricle – sends blood to
the organs
Heart Tube and Formation
• Cardiogenic mesoderm
originate from the epiblast
• Cells pass through the
primitive streak
• When head folds are evident,
a cardiac crescent is formed
• Stage where interchange of
heart regions and removal of
explants may cause heart
defects
• Different transcription factor
genes present
 Transcription Gene Nkx2.5 (homeodomain)
• Expressed in early cardiac mesoderm cells
• In Drosophila – regulator gene for formation of the heart
• Important in vertebrates - regulation
• Cre-lox labeling shows that all layers of the heart tube in
mouse embryos are formed from Nkx2.5 positive cells
• In Xenopus – overexpression will enlarge the heart
 Cardiac Mesoderm
• Induced by signals
from the endoderm
for cardiac
differentiation
• Bone morphogenetic
protein (BMPs) –
induce heart from
ectopic positions
• Noggin – prevent
heart development
• FGF8 – induce heart
formation
• Removal of Anterior
endoderm – failure of
heart development
• When foregut
starts to form,
the heart
rudiments move
underneath it
towards the
midline
• Fibronectin –
migration of the
heart rudiment
What if migration
fails?
• Cardia bifida–
formation of two
separate hearts side by
side
• These will fuse and will
form 4 layers:
• Endocardium
• Cardiac jelly
• Myocardium
• Pericardium
After fusion
• The heart tube begins to
undergo pulsations
• Controlled by the “pacemaker”
in the sinoatrial node
• Looping leads to complete
formation of atrium and
ventricle
Neural crest cells
• Also contribute in the formation
of the heart
• Septum – dividing wall between
the left and right sides of the
heart
• Atrial septum – divides the upper
chamber (right and left atria)
• Ventricular septum – divides the
lower chamber (right and left
ventricle)
Development of Cardiac Septa
• Simple heart -> four-chambered heart with separate circulation
• Pulmonary vs Aortic circulation
Looping of the Heart Tube
• Brings atria to the
anterior
• Pulmonary vein sprouts
from the left atrium
• Ventricle to the
posterior
• Atrial septa forms
toward the junction of
the ventricles
Endocardial Cushion / Atrioventricular
Cushion
• Play a vital role in the
proper formation of the
heart septa
• Appear at the
atrioventricular junction
Septum
Intermedium
• When two of the
endocardial
cushions meet ->
formation of a
septum
intermedium
• Functions in division
of the canals of the
ventricle into right
and left sides
Ventricular septum / septum inferius
• Separate the left and right
ventricle
• Controlled by Tbx transcription
factors
• Tbx5 – left ventricle
• Tbx20 – right ventricle
• Truncoconal septae – separate
the pulmonary artery from the
aorta
Truncoconal septa
• Outflow tract
The Postnatal Heart (Mouse & Humans)
• Cessation of the multiplication of cardiomyocytes
• 1st week – DNA synthesis, nuclear division -> binucleate
cardiomyocytes
• During the 1st week - Cardiomyocytes may have renewal
(regenerating) functions - “cell renewal”
• After the 1st week – lead to permanent scarring
The postnatal heart (Fish and Amphibians)
• Shows complete regeneration
• Release of retinoic acid – signal for muscle regeneration
Congenital heart defects
• Due to mutations found in genes
• Leads to a viable but defective heart
• Mouse – lethal at embryonic stages; heterozygotes are normal
• Human – lethal when associated with heterozygotes; mutations
become dominant
Mutation in NKX2.5 Gene
• Defects:
• Looping
• Atrial septa
formation
• Teratology of Fallot
Mutation in TBX5 gene
• Cause Holt-Oram syndrome –
abnormal skeletal development
• Affects primarily the
cardiovascular system – shape
and beat of the heart
• A hole in the septum between
the atria – Atrial septal defect
(ASD)
• Cardiac conduction disease
• Bradycardia
• Tachycardia