Model systems

Question 1

Why do we need model systems in developmental biology?

Answer 1

> understand how humans develop

> understand why sometimes it goes wrong

Question 2

Developmental malformations

Answer 2

= abnormalities that arise due to genetic mutations

e.g. club foot

Question 3

Developmental disruptions

Answer 3

= abnormalities caused by environmental factors or substances
e.g. phocomelia caused by thalidomide (morning sickness drugs)

Question 4

3 approaches to using animal models to study development

Answer 4

> anatomical approaches
= observing how embryos develop

> experimental approaches
= embryo manipulations + cell transplants

> genetic approaches

Question 5

Pros + cons of model systems to consider

Answer 5

> no. of embryos
> accessibility 
> cost 
> embryo manipulation 
> genetics
> gene inventory/ genome sequencing 
> similarity to humans

Question 6

No. of embryos

Answer 6

Species that generate larger no. of progenies are more useful
(Also - faster embryogenesis means faster experimental turnover)

Question 7

Cost

Answer 7

Can they be kept in labs?

Do they need lots of care?

Question 8

Accessibility

Answer 8

Externally developing embryos are more accessible

Question 9

Embryo manipulation

Answer 9

Easily manipulated embryos

e.g. removing a cell or piece of tissue -> transplanting into 2nd embryo

Question 10

Genetics

Answer 10

Is the species suitable for genetic studies?

- based on life cycle duration

Question 11

Gene inventory

Answer 11

Has the genome been sequenced?

Question 12

Similarity to humans

Answer 12

If studying a human disorder - how similar is the animal model to the human condition?
i.e. physiology biochemistry etc.

Question 13

Sea urchin

- facts

Answer 13

Fast, early development

Short life-cycle = 50 days

Large no. of progeny

Expensive

Good access - transparent + external embryos

Easy micro manipulation

Easy genetics

Genome sequenced, diploid, 21 chromosomes

Question 14

Sea urchin

- experiment

Answer 14

Hans Driesch

1.Shook a 2-celled embryo so cells parted
2. Each cell produced fully-formed sea urchin
= artificial twinning

= each cell in embryo had own set of genes + could grow into full org

Question 15

Drosophila

- mating

Answer 15

Eggs fertilised when pass from oviduct on way to being laid

Females store sperm for 2 weeks

Question 16

Drosophila

- facts

Answer 16

V short generation time = 9 days

Large no. of progeny

Easy + cheap to maintain

External embryos

Easy micro manipulation

Easy to make mutants

Genome sequenced, polytene chromosomes

Question 17

Polytene chromosomes

Answer 17

Giant chromosomes that arise from repeated rounds of DNA replication w/out cell division

May offer metabolic advantage + account for rapid growth during larval stage

Question 18

Drosophila

- experiment

Answer 18

1. Crossed white-eyed male (XwY) with pure-bred red-eyed female (XWXW)
   = F1 all had red-eyes
2. Crossed M + F from F1
   = F2 had 3:1 ratio of red:white
   = all white-eyed were male
3. Crossed F2 hybrid M + F
   = observed some white-eyed females (XwXw)

.:. 1st evidence of sex-linked recessive traits

Question 19

Nematodes
(C. elegans)
- facts

Answer 19

Fast development - 2 days

Large no. of progeny

Cheap + easy to maintain

Developing embryos can be removed + grown in lab Transparent

Easy micro-manipulation

Easy genetics - approx 1700 developmental genes

Genome sequenced
- 5 pairs of autosomes, 1 pair of sex chromosomes

Question 20

Nematodes

- experiment

Answer 20

Sydney Brenner

Gathered data to trace lineage of each of its 959 somatic cells from 1 zygote

During development 1090 cells are generated but 131 of these die to produce an adult worm comprised of 959 cells

Mapped worm’s entire NS

Question 21

Xenopus

- facts

Answer 21

Rapid development of tadpoles
- but relatively long life cycle

Large no. of progeny

Cheap + easy to maintain

Access: large eggs + tadpoles
Development easily observed

Easy micro manipulation

Genetics: easy to make transgenic line

Genome sequenced
- pseudotetraploid

Question 22

Pseudotetraploid

Answer 22

Doubled the no. of chromosomes 30mya

Question 23

Xenopus

- experiment

Answer 23

John Gurdon

1. Treated unfertilised eggs with UV to destroy genetic material
2. Isolated skin cells from adult frog OR tadpole gut epithelial cells
3. Removed nuclei from these cells and placed them in enucleated frog eggs
4. Tadpoles developed into clones of animal the nucleus came from

Question 24

Mouse
= Mus musculus
- facts

Answer 24

Relatively short generation time (for a mammal)

Reasonable no. of embryos
(6-15 litter)

Easy to maintain but expensive

Poor access as internal

Difficult micro manipulation

Easy to make transgenic and mutant mice

Genome sequenced, diploid, 21 chromosomes

Question 25

Mouse | - experiment

Answer 25

Martin Evans 1. Took ES cells from brown mouse 2. grew them in culture 3. transplanted into inner cell mass of blastocyst from white mouse 4. Chimera mouse develops made from brown and white mouse cells

Question 26

Chicken | - facts

Answer 26

Early stages of embryogenesis = fast BUT long life cycle =20 weeks Good no. of embryos Cheap Good access: external + cut hole into egg to observe development Easy to manipulate surgically Difficult to produce mutants Genome sequenced, diploid, 38 chromosomes, 1 pair of sex chromosomes

Question 27

Chicken | - experiment

Answer 27

Nicole Le Dourain Transplantations between chicken + quail embryos: 1. removed part of developing neural tube from quail embryo + transplanted into recipient chick embryo of same stage 2. Chimeric chick formed = determined that precursors in neural crest = multipotent

Question 28

Zebrafish = Danio rerio - facts

Answer 28

Short generation time = 90 days Large no. of progeny Expensive Good access: external + transparent Possible micromanipulation in early stages Easy to manipulate gene expression + can generate transgenics Genome sequenced, 25 chromosomes

Question 29

Zebrafish | - experiment

Answer 29

Large scale mutagenesis screen in zebrafish | - 1000+ genetic mutants were generated + screened for developmental defects