Introduction to Developmental Biology Flashcards
What three areas is modern developmental biology a combination of?
Embryology
Cytology
Genetics
What is the overarching aim of developmental biology?
To understand the genetic and cellular mechanims that produce a comple multi-cellular organism from a single cell
What does pattern formation require?
Differential gene expression
Signalling between cells
What are the 6 stages that pattern formation arises through?
Cell proliferation Cell migration Changes in cell shape and size Cell differentiation Cell interaction Apoptosis
What are the two major cell types in the early developing embryo?
Epithelial cells
Mesenchymal cells
What are the characteristics of epithelial cells?
Polarised Sit on a basement membrane Cell-to-cell junctions Usually have motile cilia Marker genes (i.e. cytokeratin)
What are the characteristics of mesenchymal cells?
Not polarise
Not joined to others cells (i.e. motile)
Marker genes (i.e. vimetin)
Lie within a matrix
A cell that is destined to become a square is relocated to amongst cells that are destined to become circles. The cell become a circle cell. What can you say about its cell fate commitment?
It is specified but not determined
A cell that is destined to become a square is relocated to amongst cells that are destined to become circles. The cell become a square cell. What can you say about its cell fate commitment?
It is determined
What is cell fate restriction governed by?
Cell’s genome (gene expression)
Cell’s history (factors it has been exposed to, where it has moved from)
Interaction with its neighbours
What are the advantages of using Drosophila and round worms to model normal and abnormal human development?
Easy to keep; rapid life cycle (10 days in fly, 3 days in worm)
Easy to genetically modify over multi-generations; key genes known
Fate of most or all cells known
What are the disadvantages of using Drosophila and round worms to model normal and abnormal human development?
Many aspects of development and anatomy are not conserved with humans
What are the advantages of using zebra fish and African clawed frog to model normal and abnormal human development?
Easy to keep; can add factors to the environment (water
Easy to manipulate as embryo develops outside maternal body
What are the disadvantages of using zebra fish and African clawed frog to model normal and abnormal human development?
Distant from humans; some features not shared (mammary glands)
What are the advantages of using chicks to model normal and abnormal human development?
Closer to humans
Easy to manipulate as embryo develops outside maternal body
Early embryogenesis is very similar to humans
What are the disadvantages of using chicks to model normal and abnormal human development?
Longer life cycle (4 months); transgenic strategies lag behind mice
What are the advantages of using mice to model normal and abnormal human development?
Same organ systems and many of the same diseases as humans
Relatively easy to maintain colonies; advanced transgenic available
What are the disadvantages of using mice to model normal and abnormal human development?
Embryos develop in utero
Can be expensive to generate null mutants
Models can sometimes show different phenotypes to human disease
Some cells of a frog embryo that would give rise to the gut are transplanted into the future head region and still develop into intestinal epithelial cells.
Which word best describes the cells at the time of transplantation?
a) they are specified
b) they are determined
c) they demonstrate fate mapping
d) they are differentiated
e) none of the above
b) they are determined
Differential gene expression occurs due to interaction between ___________ (working within a cell) and __________ (working between cells)
Transcription factors; signalling molecules
What are the regulatory elements that control gene expression?
Promoters
Enhancers
Inhibitors
What is an example of homeotic transformation?
Antennapedia (legs where antennae should be)
How are homeotic transformations caused?
Mutation in relevant Hox gene
How many Hox clusters do mammals have?
Four
What is it called when one gene can compensate for the loss of a related one?
Functional redundency
How would you determine the role of a gene found to be expressed in the brain?
Knockout the gene and observe the phenotype
How would you determine the role of a gene found to be expressed in the brain when it is also expressed in several other sites?
Conditional knockout
What are the main type of paracrine signalling molecules?
Fibroblast growth factors (FGFs)
Hedgehog
Wnt
Transforming growth factor-β (TGF-β)
What is a change in cell fate due to signals sent from other cells called?
Induction
What factors determine how a cell will respond to morphogens?
Other signals it is currently receiving Cell memory (past signals it has received)
What type of inhibition is the Notch signaling pathway?
Lateral inhibition
How does the Notch signalling pathway occur?
Direct interaction between the cell surface receptor (Notch) on the receiving cell and a ligand (Delta, Jagged or Serrate) on the signalling cell. When the receptor is activated, a protease cleaves part of the receptor that enters the nucleus and promotes the transcription of a particular gene
What are the three types of signalling?
Autocrine
Paracrine
Endocrine
What are the two type of receptors that paracrine factors activate and how do they induce phosphorylation?
- Those with intrinsic protein kinase activity (phosphorylates downstream factors)
- Those that use a second messenger system to activate cytoplasmic kinases
What type of recepor does fibroblast growth factors (FGFs) activate?
Receptor tyrosine kinases (RTK)
What functions of FGFs play in development?
Cell proliferation
Promotion of angiogenesis
Activation/suppression of other pathways
What is the mechanism by which FGFs activate/supress gene transcription?
FGFs bind to the receptor tyrosine kinase which activates a G-protein which activates RAS which activates RAF which activates a MAP kinase which activates ERK which phsophorylates a transcription f1actor
Where is Fgf8 mRNA expressed in a chicken embryo?
Outer epithelial of limb bud
What happens when a bead carrying Fgf8 is implanted into the embryo?
An extra limb can form
Which of the following is an example of a morphogen?
a) a transcription factor that can bind more than one target gene
b) an endocrine signal that can influence how cells behave
c) a diffusible protein that influences cell fate
d) a cell that induces its neighbours to follow a developmental fate
c) a diffusible protein that influences cell fate
What receptor does transforming growth factor-β (TGF-β) use?
Serine/theronine kinase receptor
How does TGF-β influence the transcription of a gene?
Activation of the receptor leads to activation of Smad proteins that combine to form a dimer which then combines with a cofactor in the nucleus and interacting with the DNA
What function does TGF-β play in development?
Cell specification
Regulating extracellular matrix formation
Cell division
Cell death
What can make TGF-β functionally redundant?
Bone Morphogenetic Proteins (BMPs)
What are essential regulators of chondrogenesis (cartilage formation)?
Bone Morphogenetic Proteins (BMPs)
Which signalling pathway is essential for gastrulation?
Wnt signalling pathway
How does the Wnt pathway influence gastrulation?
It defines that dorsal side of the embryo; assists with neural tube formation, cells proliferation, polarity and differentiation
How does Hedgehog activate transcription?
Hedgehog binds to a patched (PTC) receptor, preventing it from inhibiting SMO meaning that SMO can prevent the phosphorylation and deactivation of the transcription factor Gli. Gli can then enter the nucleus and promote transcription
What are the two important drivers of morphogenesis?
Direct cell-to-cell adhesion
Cell migrationl
How can boundaries between cells be created?
Cells having different types and different amounts of cell surface molecules called cell adhesion molecules
What type of cadherin is found on most early embryonic cells and later in epithelial tissues?
E-cadherins
What type of cadherin is found on neural cells?
N-cadherins
What type of cadherin is found on placental cells?
P-cadherins
True or False:
Both epithelial and mesenchymal cells migrate
True
Epithelial as sheets or tubes
How do epithelial cells migrate?
The polarity of the cell changes due to signals. Actin filaments assemble at the leading edge of the cell and provide mechanical force. The cell interacts with extracellular matrix, particularly integrins which pull the cell along. Myosin also provides motile force along the actin filaments
Which experiment below shows that Fgf4 is sufficient for limb development in the chicken embryo?
a) Implant a bead expressing Fgf4 and observe an extra limb forming
b) Knock out the gene and note loss of limb during development
c) Show that Fgf4 is expressed in the forming limb using in situ hybridisation
d) All of the above
a) Implant a bead expressing Fgf4 and observe an extra limb forming
b) is incorrect because it shows that it is required not sufficient
What are the four types of cell potency?
Totipotent
Pluripotent
Multipotent
Unipotent
What are individual cells called during the cleavage stage?
Blastomeres
What cadherin mediates compaction at the 8-cell stage of cleavage?
E-cadherins
What is the compacted ball of cells called during cleavage?
Morula
When the inner cells move to one side of the morula, creating a cavity, what is the ball of cells called?
Blastocyst
Which part of the blastocyst is ES cells found?
Inner cell mass
The cells that move to one side of the morula are called what?
Inner cell mass
The cells on the outside of the blastocyst are called what?
Trophoblast
What pluripotency factors do cells in the inner cell mass express?
Oct4, Nanog and Sox2
A blastomere exposed to Oct4 will become what?
Inner cell mass
A blastomere exposed to Cdx2 will become what?
Trophoblast
An inner cell mass cell exposed to Nanog` will become what?
Epiblast
An inner cell mass cell exposed to Gata 6` will become what?
Hypoblast
What must a blastomere be exposed to in order to become an epiblast cell?
Oct4 and then Nanog
The first cells to migrate through the primitive streak and displace the hypoblast become what?
Endoderm
The second cells to migrate through the primitive streak and displace the hypoblast become what?
Mesoderm
Where is the primitive streak found?
The caudal (tail) end of the embryo
What are the two key organisers that develop in the early mammalian blastocyst?
- A specialised group of cells in the hypoblast (Anterior Visceral Endoderm (AVE) in mice)
- Primitive streak
What is the primitive node?
A dynamic mass of cells at the anterior tip of the primitive streak
Which signalling molecules are responsible for the positioning of the primitive streak?
Nodal, FGFs and Wnts
What signalling molecules are highest at the posterior?
Wnts, BMPs and FGFs
What signalling molecules are highest at the anterior?
BMP and Wnt antagonists
From which structure in the late blastocyst does the entire embryo develop?
Epiblast
What parts of the body does the ectoderm differentiate into?
Skin and its derivatives Nerves and sensory systems Pituitary gland and adrenal medulla Jaw and teeth Neural crest cells