Model systems

Question 1

Why do we need model systems in developmental biology?

Answer 1

To understand how humans develop and to understand why sometimes it goes wrong.

Question 2

What did thalidomide cause and what was it used for?

Answer 2

It was used as a morning sickness drug for pregnant women that cause limb development disruption- phocomelia.

Question 3

What is the difference between development malformations and developmental disruptions?

Answer 3

Malformations are genetic mutations and disruptions are environmental factors.

Question 4

What is cleft palate caused by?

Answer 4

Genetic and environmental defects.

Question 5

What is club foot caused by?

Answer 5

Genetic defects.

Question 6

What is spina bifida?

Answer 6

When the neural tubes fail to close.

Question 7

What are the three approaches in which animal models are used to study development?

Answer 7

Anatomical approaches, experimental approaches and genetic approaches.

Question 8

What are the pros and cons of animal models to consider?

Answer 8

The number of embryos, accessibility, cost, embryo manipulation, genetics, gene inventory/genome sequencing, similarity to humans.

Question 9

In terms of the embryo, what makes sea urchins good model organisms?

Answer 9

Embryos are transparent and develop in the external environment - easier to study and manipulate,

Question 10

In terms of development, what makes sea urchins good model organisms?

Answer 10

Development is fast - 5 days after fertilisation, the embryo hatches to become a pluteus larva capable of still feeding.

Question 11

What are features of drosophila that makes them useful models?

Answer 11

The eggs are fertilised when they pass from the oviduct on their way to being laid, females can store male sperm for up to two weeks after mating, eggs are fertilised and immediately laid and the whole process from egg to sexually mature fly only takes 9 days.

Question 12

How are drosophila stored?

Answer 12

They are kept in jars with fluid at the bottom and a stopper at the top. Hundreds can be maintained at one time.

Question 13

What are the benefits of using nematodes as animal models?

Answer 13

They have fast development, they are small, transparent, developing embryos can be removed from the adult female and grown in the lab, hermaphrodite (male and female sex organs).

Question 14

What are the practical benefits of using nematodes?

Answer 14

They are easy and cheap to maintain, the mutant lines can be frozen down to maintain stocks, they are simple (only 959 cells), and by following cell divisions with a microscope the complete cell lineage has been made.

Question 15

What does it mean that nematodes are hermaphrodites?

Answer 15

They are females that make their own sperm for a short time and then switch to making oocytes and they are capable of self fertilisation - however some males do also exist.

Question 16

What are the benefits of using the xenopus (frog) as an animal model?

Answer 16

It has large eggs and embryos and develops outside of the maternal environment. The development of embryos and tadpoles is rapid.

Question 17

What is the disadvantage of using the xenopus as an animal model?

Answer 17

The complete life cycle is relatively long, despite the development of embryos and tadpoles being rapid.

Question 18

What are the practical benefits of using the xenopus as an animal model?

Answer 18

It is easy and cheap to maintain - it can be kept in small tanks of tap water.

Question 19

What work was John Gurdon involved in with xenopus embryos?

Answer 19

He took unfertilised eggs and treated them with UV to destroy the genetic material in them, and then isolated skin cells from adult frogs, removed the nuclei and let the enucleated cells grow into clones.

Question 20

What are the benefits of using mice as animal models?

Answer 20

They are mammals - can be used to study human development and disease closely, they have a relatively short life cycle for a mammal, development is internal, they have well characterised genetics, they have embryonic stem cells and then can be easily genetically manipulated.

Question 21

What is the problem practically with using mice as animal models?

Answer 21

They are kept in racks of cages in a designated facility with trained staff - high cost.

Question 22

What is the progeny size of mice?

Answer 22

6-15 pups per litter.

Question 23

What significance did Martin Evans have with mice animal models?

Answer 23

He was the first person to isolate mouse embryonic stem cells and culture them.

Question 24

What are the benefits of using chickens as animal models?

Answer 24

You can see most stages of development by cutting a hole in the egg shell. Many aspects of development are similar to humans.

Question 25

What are the practical benefits of using chickens as animal models?

Answer 25

They are easy to incubate on a large scale without high cost.

Question 26

What are the downsides of using chickens as animal models?

Answer 26

It is tricky to generate transgenic chicks and they have a relatively long life cycle (20 weeks).

Question 27

What are the benefits of using zebrafish as animal models?

Answer 27

There is rapid embryogenesis, they have external development and are transparent until just after hatching, they can be genetically manipulated and they have a duplicated genome.

Question 28

What are the practical benefits of using the zebrafish as an animal model?

Answer 28

They are easy to produce transgenics/morpholinos and they are cheaper to keep than the mouse (but still expensive).

Question 29

What is an example experiment for the zebrafish being used as an animal model?

Answer 29

Large scale mutagenesis screen by Christiane Nusslein-VOlhard to screen for developmental defects.

Question 30

Why is development time after fertilisation important as an animal model?

Answer 30

Experimental turnover will be much faster.

Question 31

What determines whether a species is suitable for genetic studies?

Answer 31

The duration of the life cycle - if the life cycle is long then the animal is less useful as the turnover is slower so you have to wait for the animal to reach maturity to breed and produce more animals to study.

Question 32

What was an early experiment with the sea urchins in developmental biology?

Answer 32

Hans Driesch - 1885 - took a two celled sea urchin embroy and shook it so the cells parted. The cells were separated and found that each cell produced a fully formed normal sea urchin.

Question 33

What was an early developmental biology experiment with drosophila?

Answer 33

Thomas Morgan noticed a drosophila had white eyes instead of red and cross bred these to see how the genes were passed on. He linked genes with chromosomes.

Question 34

What was an early experiment involving nematodes?

Answer 34

Sydney Brenner lineage traced somatic cells from a zygote and identified genes in cell death, and carried out research that led to the mapping of the worms nervous system.

Question 35

What was an early experiment done with the frog xenopus?

Answer 35

John Gurdon treated eggs with UV to destroy genetic material and isolated skin cells from an adult frog and removed the nuclei and put them in the empty eggs and let them develop. Clones were formed.

Question 36

What was an early experiment with mice?

Answer 36

Martin Evans and Gail Martin discovered mouse embryonic cells. Knockout mice by injection of genetically modified ES cells into mouse blastocysts.

Question 37

What was an early experiment with chicken?

Answer 37

Nicole Le Douarin developed an embryo manipulation technique to produce chimeric embryos. Determined that the precursors in the neural crest were multipotent.

Question 38

What was an early experiment with the Zebrafish?

Answer 38

Christiane Nusslein-VOlhard set up a large scale mutagenesis screen of zebrafish embryos and screened for developmental defects. There was phenotype rescue of the alb b4 mutant zebrafish line using genome editing technology.