L21 model organisms for studying development

Question 1

what is developmental biology?

Answer 1

1. study the process which organisms grow and develop
2. focus on growth, differentiation, morphogenesis (creation of shape)
3. understanding congenital malformations
4. understanding regeneration, repair, ageing and cancer

Question 2

when is it called an embryo?

Answer 2

at 8 weeks

Question 3

when is it called a foetus?

Answer 3

at 12 weeks

Question 4

when is the developmental period in mammals?

Answer 4

from fertilisation to birth (differs between other classes of animals)

Question 5

what is an embryo?

Answer 5

the developing organism (foetus once fully formed) develops from a single cell to a complex animal with trillions of cells that has to function before it is fully formed

Question 6

what is differentiation?

Answer 6

how a single cell gives rise to hundreds of different types

Question 7

what is morphogenesis?

Answer 7

how cells form ordered structures to build tissues, organs and organisms

Question 8

what is growth?

Answer 8

how our cells know when to divide and when to stop

Question 9

what are the 3 general approaches to studying development?

Answer 9

1. anatomical
2. physical manipulation
3. genetic

Question 10

what is a model organism?

Answer 10

a well established experimental biological system

Question 11

what are humans more similar to?

Answer 11

The mouse more than a fly or worm

Question 12

what gene is responsible for eye development?

Answer 12

the Pax6 gene

- can trigger eye development in Drosophila

Question 13

what are the 2 key molecules in eye development?

Answer 13

1. opsins

2. crystallins - formation of the lens

Question 14

what gene is responsible for cardiac evolution?

Answer 14

Nkx2.5 gene

Question 15

what happens when the Nkx2.5 is mutated?

Answer 15

1. causes a small heart with small chambers in mice

2. causes holes in the heart in humans

Question 16

what was the last common ancestor of humans and flies?

Answer 16

Ikaria wariootia

Question 17

characteristics of ikaria wariootia

Answer 17

1. worm like structure
2. oldest known bilaterian (550 million yrs old)
3. size of rice grain
4. no limbs, eyes, heart ( did have ancestral genes to make these complex structures)

Question 18

what is temporo-spatial colinearity?

Answer 18

the oder of genes on a chromosome corresponding to the order of expression during development and placing on the body

Question 19

why is Drosophila useful?

Answer 19

1. genome sequenced
2. most genes homologous to mammals
3. mutants available (X- ray and chemically induced)
4. short life cycle
5. many easily accessed larvae
6. understand the basic gene networks that regulate early body plan

Question 20

what can abnormal development teach us?

Answer 20

1. about normal development

2. studying what happens when a gene is missing tells us what it does

Question 21

why are zebrafish useful?

Answer 21

1. genome sequenced genetically similar to man
2. fundamental development processes similar to mammals
3. easy to manipulate genetically- can access the eggs
4. easy to manipulate experimentally (physically and chemically)
5. can regenerate body parts
6. transparent embryos

Question 22

why are amphibians useful?

Answer 22

1. have large embryos, easily manipulated
2. anatomically more similar to mammals
3. can regenerate body parts
4. not as popular since zebra fish

Question 23

why are birds useful?

Answer 23

1. anatomically most similar to mammals (organ level)
2. large accessible eggs
3. easy to manipulate and image
4. very complex genetics

Question 24

why are mice useful?

Answer 24

1. genome sequenced
2. similar to humans
3. large number of mutants available
4. can manipulate genome
5. relatively rapid life cycle
6. relatively affordable?

Question 25

disadvantages of mice?

Answer 25

1. hard to physically manipulate as they develop in utero

2. cost

Question 26

what genetic tools are available to us?

Answer 26

1. morpholinos, siRNA
2. chemical mutagenesis (ENU)
3. transgenesis (transient / gremline)
4. single gene knockouts and knockins (ESC)
5. conditional gene knockouts (knockins)
6. CRISPR

Question 27

why do we need animal models?

Answer 27

1. can’t use humans for experiments
2. can’t model disease processes in cell culture
3. can’t test toxicity of new drugs or treatments in cell culture
4. can’t model complex development or ageing processes in cell cultures

Question 28

what are the limitations in using humans?

Answer 28

1. ethical reasons
2. very complex genetics
3. limited access to human embryos

Question 29

what is a human organoid?

Answer 29

self organising three- dimensional cell cultures derived from pluripotent stem cells (including ESC and hiPSC)

Question 30

what are stem cells used for?

Answer 30

to recapitulate early stages of development in a dish and have been created for many organs

Question 31

potential of organoids?

Answer 31

1. disease modelling
2. drug efficiency testing
3. organ replacement therapy
4. drug safety testing

Question 32

what makes a good model for developmental research?

Answer 32

1. genome sequenced
2. readily available (source/stock)
3. large number of offspring per gen.
4. rapid development rate to maturity
5. easily manipulated and genetically tractable
6. anatomically resembles a human (organ/tissue/cellular level)