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Lecture 20

HMB321H1 Lecture Notes - Lecture 20: Heart Development, Congenital Heart Defect, Genetic Testing

Human Biology
Course Code
Maria Papaconstantinou

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30 MAR 2011
HMB321 L20: Zebrafish & Cardiovascular Disease (CVD)
Why Study Heart Development?
-We are born with only a set number of heart muscles, which, over time, will senesce and we
eventually encounter issues (e.g. CVD)
Need a greater understanding of heart development
-We need to understand how heart cells are in the embryo => can we learn something like this
to add something endogenous into the heart to aid these issues
-Adult heart muscle cells have different components than embryonic
-Understanding gene programming can tell us how to turn off certain functions that are
detrimental, though occur in adult heart cells
Heart development: Complex Morphological Process
-Once cells are specified, must organize into a tube
-While the embryo is growing and pumping blood through, looping will occur (hence
the fact that our blood pumps through left side first)
Ventricular Septal Defect
-In some cases, incomplete septation occurs leaving an obvious hole in the septum
-Unlike in wt heart, deoxygenated and oxygenated blood can be mixed
-Can decrease survival due to reduction of oxygenated blood perfusing through body
Model Organisms to Study Heart Development
-Fruit flies
-Have a single pulsating tube that moves lymphatic fluids throughout the body
(analogous to the heart and the blood that flows through)
-Mammalian heart (mice)
-Analogous to our heart, i.e. Atria, ventricles, etc
What can the fruit fly “heart” (simple tube) teach us?
-Tinman gene (unlike wt heart => heartless flies; no D/V structures)
-Tried to find vertebrate homologs of Tinman using RNA in situ hybridization
-Nkx2.5 is the vertebrate homolog => used for migration of specified cells to the
midline to form a heart tube, etc
-In mouse, fly, vertebrates
Nkx2-5 KO mice
-Tried KO mice of the Tinman homolog => found that there was severe defects in mice
cardiovascular development (prenatal death)
--/- form no left/right side ventricle
-Tinman homologs is also essential in mouse development and is important for higher
organisms, e.g. Mice
Elaboration of “beating tube”
-Gene that was first discovered int eh fly => important in vertebrates
-Mutation of this gene in children => congenital heart defects
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