L21-23 Vertebrate Developmental Biology & Congenital Malformations Flashcards
Morphogenesis
The development of morphological characteristics (i.e. shape)
Axis formation is the establishment of the…
Body plan
An organism has 3 key axes…
- Anterior - Posterior 🐥
- Dorsal - Ventral ↕
- Left - Right ↔
Key genes involved in body axis formation in humans are…
Hox (homeobox-containing) genes
Long range signalling important to development occurs via…
Paracrine signalling
The embryo is patterned by long range signal molecules known as…
Morphogens (which activate Hox genes)
Morphogens control the position of…
Specialised cell types
Different genes are activated at different…
Concentrations (of signalling molecule)
Morphogens move by…
Passive diffusion
The Bicoid gradient in fruit flies establishes…
Anterior - posterior polarity
Vertebrates are:
a) Bilaterally symmetric
b) Bilaterally asymmetric
c) Multilaterally symmetric
d) None of the above
b) Bilaterally asymmetric
Left and right sides are not identical (e.g. internal organs)
Left-right axis formation occurs due to the specific activation of signalling pathways on only the ( left / right ) side
Left
Signal molecules are wafted from right to left by…
Cillia 🌬
Disturbed laterality can have severe consequences, except when…
Laterality is simply reversed 🙂🙃
Hox 6 is the signal for ‘make ribs’, whereas Hox 10 signals ‘stop ribs!’. In snakes, which of these genes is inactive?
Hox 10 🐍
The same morphogens (signalling molecules) pattern…
Different parts of the embryo
The apical ectodermal ridge (AER) is critical to…
Limb development
The importance of AER can be seen in Thalidomide affected babies…
Thalidomide destroys AER, resulting in disrupted limb development
The AER produces growth but doesn’t specify…
The type of growth (i.e. what will grow)
Dorsal - ventral patterning is:
a) comparatively simple
b) highly complex
c) absent in humans
d) absent in mammals
e) disrupted by Thalidomide
b) highly complex
Dorsal - ventral patterning is involved with the formation of the (2)…
Spinal cord and brain 🧠
Developmental biology can help us to understand:
a) Growth and differentiation
b) Morphogenesis
c) Congenital malformations
d) Initiation and construction
e) All of the above
e) All of the above!
Human lifecycles feature a period of development which is relatively…
Long
Development is…
The period between fertilisation and birth
An embryo is…
The developing organism
The fetus is…
The developing organism once fully formed
Three approaches to studying development…
- Anatomical
(what do things look like? how are cells positioned properly, and which cells go on to form mature structures, e.g. arms) - Manipulation
(removal, transplant or drugs to interfere with development) - Genetic
(how do genes control development? how different genes integrate instructions and how specific mutations lead to congenital malformations and disease)
Model organisms can be used to understand development in humans as the…
Important genes to development are conserved between organisms
Nomenclature of genes usually reflects…
The effect of their dysfunction in the mutant
5 animal models for studying development
- Drosophila
- Zebrafish
- Amphibians
- Chickens and quail
- Mice
Why do we need animal models?
- We can’t experiment on humans 🙅♀️
* Cell cultures can’t model disease processes or development or ageing etc.
In the future animal models may be replaced by…
Human organoids
Human organoids are…
3D self-organised cell cultures derived from stem cells. They could be used for research, drug testing and organ replacement therapy
What makes a good model organism? (6)
☑️Sequenced genome ☑️Anatomical resemblance ☑️ Rapid development ☑️High fecundity (lots of offspring) ☑️Easy to manipulate and modify genetically ☑️Readily available
Choosing a model organism depends on…
The question being investigated. Relevant factors to consider include:
- Time span
- Manipulation
- Similarity to humans
- Ethics
- Costs
Drosophila have large and easy to access…
a) Bodies
b) Genes
c) Larvae
d) Bank accounts
c) Larvae
This makes them useful for studying development
The study of abnormal development tells us about…
Normal development
Zebrafish regenerate…
Many body parts
Zebrafish embryos are useful as they are…
Transparent and can develop outside the mother’s body
Zebrafish have many advantages as a model organism. However, they cannot be used to study…
Lung development
Amphibian embryos are…
Big and easy to manipulate
Amphibians have ( longer / shorter ) lifecycles than zebrafish
Longer 👴🏼
Amphibians are ( more / less ) expensive than zebrafish
More $$$
Which of the following is not true of chicken and quail as developmental models?
a) Large, accessible eggs
b) Anatomically similar to mammals
c) Easy to manipulate
d) Short lifecycle
d) Short lifecycle
Their lifecycle is long compared with other model organisms
What are the main disadvantages of mice as model organisms for studying development?
☹ Difficult to manipulate (young are gestated)
☹ Expensive
☹ Ethical issues (vertebrate mammals)
The organism of choice for most development studies is…
- Zebrafish
- Chimpanzee
- Mice
- Chicken or quail
- Yeast
- Drosophila
- Amphibians
- Grapefruits
- Mice 🐭
Congenital malformations are malformations which are…
Already present at birth
Most congenital malformations occur:
a) after birth
b) first trimester
c) second trimester
d) third trimester
b) first trimester
Usually within the first 10 weeks during embryogenesis
Congenital malformations result from the disruption of…
Normal development
Congenital malformations have causes that are both…
Genetic and/or environmental
Genetic causes of congenital malformations include (4)…
- Single genes
- Multi-gene interactions
- Chromosome defects
- Syndromes (combinations)
Environmental causes of congenital malformations include (5)…
- Drugs (prescription or recreational)
- Maternal diabetes
- Pollution
- Dietary deficiencies or excesses
- Fever
Under the anatomical approach, congenital malformations can be studied using (2)…
Histology and observing gross morphology
A genetic approach to studying congenital malformations may involve (4)…
- Visualising mRNA or proteins
- Observing levels of gene expression (qPCR, western blot)
- Disruption (knockout, knockdown)
- Ectopic expression (knockins, transgenes)
Lp (loop tail) mouse has…
Neural tube defects
Lp mouse is a model for…
Spina bifida in humans