Lecture 17 - Introduction to development Flashcards
Describe the process of development
Development begins with positional information (Cell signalling)
* Differentiation (differential gene expression)
* Morphogenesis (Growth/changes in cell shape/cell movement)
This process describes the development from a zygote to an organism
Development is controlled by cell proliferation and cell death as well as cell signalling (Positional information)
Describe some of the positives and negatives of various model organisms (development)
There are range of model organisms available to answer questions in developmental biology. The choice depends on the experimental question. Most processes are regulated with common genetic and developmental mechanisms.
- The purple sea urchin - Strongylocentrotus purpuratus
- Nematode worm - Caenorhabditis elegans
○ transparency – track individual cells
○ grown in large numbers
○ can be easily screened for effects of novel drugs
○ particularly useful the study of ageing processes
○ also used to study neural development
○ comprehensive connectivity map and only 302 neurons and ~7000 synapses. - Fruit fly - Drosophila melanogaster
○ rapid development
○ small genome size
○ availability of developmental mutants - Zebrafish - Danio rerio
○ small and robust
○ transparency – track individual cells
○ cheaper to maintain than mice
○ break of daylight triggers mating in zebrafish (many other fish only lay eggs in the dark)
○ hundreds of offspring at weekly intervals providing an ample supply of embryos to study - African clawed toad - Xenopus laevis
○ large oocytes
○ cell-free extracts, which offer plenty of material (protein, DNA, RNA, etc) for biochemical studies and
○ easiness in microinjection
○ cell cycle synchrony
○ conserved molecular mechanisms. - Chicken – Gallus gallus domesticus
○ ease with which cells and tissues can be labelled, transplanted and cultured
○ similarity to mammalian systems
○ access to the egg for imaging and manipulation - Mouse – Mus musculus
○ genome is similar to the human genome (99%)
○ a good genetic/molecular toolbox is available
○ ease of making transgenic models using ES cells
○ the animal’s small size facilitates large scale/high throughput studies making it a cost-efficient model.
Describe early embyonic development in xenopus egg.
The unfertilised egg consists of the animal and vegetal hemisphere
Upon fertilisation there fertilisation undergoes cleavage until it reaches the 16 cell stage
* Cleavage 1 and 2 are perpendicular and (equal holoblastic) but the nuclei are displaced (animal ward)
* Cleavage 3 is perpendicular/equatorial but unequal holoblastic
* This gives rise to a more rapidly dividing animal pole
Gastrulation can then occur - cell movements which form the gut and three primary gem layers.
Morula -> Blastula->Blastopore formation
The main functions of gastrulation is to form the gut and the primary germ lagers
1. Endoderm - gut, liver, lungs
2. Mesoderm - skeleton, muscle heart, blood
3. Ectoderm - skin nervous system
The above is in vertebrates which is slightly different to in insects. The main difference between the two is the CNS in vertebrates is found on the dorsal side compared to the ventral side in insects.
What is the importance of positional information in regards to development?
Cell fates determined by signals received from other cells - induction
* Direct cell-cell contact
* Induction at a distance – diffusible signals
Induction - vertebrate eye
Eyes begin as a pair of diverticula (pouches) from the lateral aspects of the forebrain
-Develop into optic cup - forms future retina
-Invaginated ectoderm forms the lens
-Overlying ectoderm forms cornea
Name some important signalling pathways in development.
- TGFβ receptors - Axis specification
- RTKs - Migration and proliferation
- Wnt receptors - Para-segment boundaries
- Hedgehog receptors - Limb development
Notch (delta receptors) - Cell fate decisions in the CNS
What are morphogens and how do they effect development?
The French flag model is visual description of how the concentration of a morphogen effects cell definition. Each cell has the potential to differentiate into blue, white or red. In order to maintain a gradient at steady state there has to be a ‘sink’ active degradation of the morphogen.
What are the morphogens involved in limb development?
A posterior-anterior gradient of a morphogen specifies digits in the vertebrate limb
AER (Apical Ectodermal Ridge)
* required for limb outgrowth
secretes Fibroblast Growth Factor (FGF) family proteins
ZPA (Zone of Polarising Activity)
* Controls anterior-posterior digit formation via induction
Two experiments were done to determine the signals
* A ZPA from a donor limb bud was transplanted into a host limb bud (mirror image)
A pellet of cells expressing Shh, Implanted into the anterior of a developing limb bud can induce mirror image digit formation
Describe the process of two way induction in kidney development.
An invagination from the gut called the ureteric bud is the beginning of the formation of the kidney. Metanephric blastema surrounds the bud. Mesenchyme induces bud branching. Mesenchymal condensations form. Bud induce mesenchyme-epithelium transition to form tubules.
GDNF is secreted by the mesenchyme. Ret and GDNFR are expressed on the ureteric bud (co-receptors)
Leukaemia inhibitory factor (LIF) may be the ureteric bud signal
