Cardiac Developmental Biology: Foundations and Early Mechanisms

Question 1

Why is fly used as heart model if so distant?

Answer 1

gene mutations that are found in humans and some of the dysfunctions known in humans, can still be observed in this distant organism
- can look for modifiers that either cause a more severe or less severe phenotype and look at new routes in therapeutic development

Question 2

Zebrafish as a model for heart

Answer 2

V different myocardium with only 2 chambers (atrium and ventricle).
It lacks the separation into venous and pulmonary and body circulation.
Pressure system is also different as heart also pumps against the gill so resistance heart experiences is different to the mammalian system
- useful though as there are several mutations introduced in the heart of the fish, which are revealing phenotypes observed in the mammalian heart
- HR in fish, similar to human so in some aspects electrophysiology is a better model in fish

Question 3

Mouse heart as a model

Answer 3

Mouse heart and human very similar but difference in beating rate.
Human-60, mouse -500bpm
Reflects some differences in ion channel expression. Gene mutations e.g. long QT which affect conduction very severely in human but barely in mouse.

Question 4

Main strengths of zebrafish model

Answer 4

• Transparent so can follow development of individual cells
• Visualise myocardium using microscope - can do optical electrophysiology v easily
• Development v fsat - 24hs from fertilisation to angiogenesis, in 3 days larvae are fully able to move around, another 3 months till they can have offspring
  Low cost model - much cheaper than mice
  Barely any disadvantages

Question 5

African claw frog as a model

Answer 5

Good for experimental manipulations?
BUT
-genetics not possible

Question 6

Best model?

Answer 6

Mouse
Because mammalian system so closely related
- Large amount od time before embryo actually implanting into uterus - 4 and half days. Time after implantation till orgagenesis is relatively fast

Question 7

Medio-lateral axis of mesoderm

Answer 7

• Most medial is the chordamesoerm which goes on to form the notochord which during embryonic development is an organ that provides stability and then will be substituted by the vetebrae
  
  • Adjacent is paraxial mesoderm which forms muscle tissue and bone tissue of the back. The somites are adjoining all the bone structyres
  • Further lateral is intermediate mesoderm , which forms the kidneys.
    Myocardium is one of the most lateral ones that is formed. The posterior of it forms of the blood