Post embryonic development Flashcards
What does differential growth lead to?
Differences in SHAPE
What are the 3 ways that growth can occur?
1) Proliferation
2) Cell enlargement
3) Accretion
What is cell proliferation?
Cell divsion
How does cell enlargement cause growth?
Example?
Increase in cell size –> increase in organ size
Happens in cardiac hypertrophy (heart increase in size by increasing in cell size)
What is accretion?
Example?
ECM being laid down outside of cells –> allowing them to grow
Bone
What drives the cells cycle?
How?
Cyclins and CDKs:
- Different cyclins drive different parts of the cell cycle
- Different cyclins activate different CDKs
- CDKs control other proteins by PHOSPHORYLATING them
How do different tissues grow in relation to each other?
They grow differently - all inherit their OWN individual growth programme
Describe the initial cell cycle of the drosophila
- Nuclei initially go through initial rapid divisions (no G1 or G2 phases)
- At cycle 14: cell cycle slows and G2 stage is inserted into the cycle
- Nuclei move to the periphery of the embryo and become cellularised
As well as the insertion of G2 at cycle 14, what else happens in drosophila development?
Mitotic domains develop:
- Each have their OWN cell cycle programme (divide differently)
- But the cells within each domain behave in the SAME way
How are mitotic domains in the drosophila controlled?
By STRING expression - which activates CDKs
What kind of protein is String?
A PHOSPHATASE
How is String expression controlled?
How?
By the patterning genes that set up the AP and DV axis of the embryo (gap,pair rule, segment polarity, D/V)
DIRECT LINK between the patterning genes and PROLIFERATION via STRING expression
What happens in the mesoderm in relation to string expression (exception)?
Why?
Expresses string EARLY but DOESN’T undergo cell division
Due to protein TRIBBLES - blocks string function
What does the blockage of String by Tribbles allow?
The INVAGINATION of the mesoderm into the embryo, which must occur when the cell is dividing and not moving
What are the experiments that try to determine how the organ knows how big to grow?
What are the results?
1) Graft limb bud from one species to another
- -> INTRINSIC pattern of growth MAINTAINED
- -> Limb develops that doesn’t fit the pattern of the rest of the body
- -> INTRINSIC control
2) Transplant an additional thymus
- -> Retain their original size, more than original amounts of thymus tissue
3) Transplant additional SPLEEN
- -> Become HALF the NORMAL size (stop growing when there is a certain amount of total spleen tissue present)
What type of growth control controls the size of organs?
Intrinsic or extrinsic, depending on the organ
What is important in determining the size of specific structure?
The absolute dimensions, not the cell number
What determines cell size?
How does this impact on the size of the animal?
Ploidy (the amount of copies of the genome that are present in the cell):
- Cells in haploid are smaller than diploid which are smaller than triploid
- BUT, the size of the animal will be the same
What determines the size of the organ?
How?
MORPHOGENS
NOT growth factors
What is the steepness of the morphogen gradient determined by?
The size of the organ
NOT the cell number
What are the 2 pathways that impact on organ growth/size?
1) TOR pathway
2) Hippo pathway
How does TOR impact on organ size?
Impacts on CELL SIZE
What is an inhibitor of TOR?
What does this cause?
Rapomyosin
Causes cells to be SMALLER
What happens when the Hippo pathway is active/inactive?
When the pathway is INACTIVE:
- The transcription factor is present in the NUCLEUS
- -> Stimulates the growth and survival of cells
When the pathway the ACTIVE:
- The transcription factor is EXCLUDED from the nucleus
What does the Hippo pathway control?
The organ size
What is the transcription factor of the Hippo pathway?
Yki - in drosophila
Yap/Taz in vertebrates
What is the vertebrate analogue of Hippo?
Mst 1/2
What do Hippo/Mst1/2 do?
Integrates various signals to create a ‘stop growing’ signal
When is the Hippo pathway INactivated?
When not enough cells are around - cells are stretched –> mechanical stresses on the cell
- TF in the nucleus, growth
When is the Hippo pathway activated?
When there is lots of cell-cell contact
- TF excluded from the nucleus, lack of growth
What happens in a Hippo mutant?
What does this cause?
Loss of GROWTH RESTRICTION
- -> Yki in the nucleus
- -> overgrowth of the imaginal disc
What happens when Mst1/Mst2 is mutant in the liver?
Tissue specific
Yap/Taz in the nucleus
–> Oversized liver
What is size controlled by?
The RATE and DURATION of growth
What is the the size of drosophila adult dependant on?
The size of the larva
What affects the duration and rate of larval growth?
How?
Insulin signalling
Lots of insulin –> age quicker
What occurs in insulin deficient flies?
Smaller cells
Fewer cells
Larva grow less
Flies are smaller
What is IGF involved in?
AGING as well POST-EMBRYONIC growth
What drives post-embyronic growth in mammals/humans?
Hormones:
- IGF1
- IGF2
- GH
- Maternal influence
What drives the production of IGF driven by in mammals?
Where?
GH
Locally in LARGE amounts
How does GH repress its own production?
1) Via inhibiting a growth hormone releasing hormone (GHRH)
2) By stimulating the production of SOMATOSTATIN - an inhibitor of GH
What happens to IGF mutants in mice?
Mice are much smaller in size
How does the maternal environment influence growth?
1) Size of the offspring is influenced by the size of the mother (but in the end, grow to be a similar size)
2) Mental conditions can affect the growth in the womb - has dramatic consequences later on
What is low birth weight associated with?
CHD
Where are the adult structures of the fly in the larva?
In the IMAGINAL DISCS
What is the difference between signalling in embryogenesis and in post embryonic development?
Embryogenesis - short range signals
Post embryonic:
- Long-range signals, more global
- More input from the environment and the CNS –> resulting in the production of particular hormones that drive post embryonic growth
What is Ecdysis?
Molting of the larva in between instars
Why does Ecdysis happen?
- Stretch receptors activated
- Activation of PTTH
- Drives the expression of ecdyson from the protothroratic gland
- Drives the process of malting
What is the final pupation of the drosophila controlled by?
How is tha
Ecdyson
What happens during the final pupation/metamorphosis?
1) Environmental cues: light, temperature, feeding act on the brain - are integrated, which lead to the production of PPTH
2) PPTH acts on the protothoratic gland
3) Release of ECDYSON - lead to the final stages of metamorphosis
What determines if the animal will undergo metamorphosis?
Ratio between Ecdyson (increased in response to environmental cues) and Juvenile hormone
How does a tadpole turn into a frog?
1) Environmental cues (temperature, light, nutrition) act on the HYPOTHALAMUS
2) Release of corticotropin releasing hormone (CRH)
3) CRH acts to produce thyroid stimulating hormone (TSH)
4) TSH leads to the production of thyroxin (T4T3) –> leads to metamorphosis
What feedback loop is thyroxin involved in?
POSITIVE feedback loop:
- Certain amount of thyroxin will feedback on the production of CRH and TSH
- To push the system forwards, REGARDLESS of a threshold of thytoxin
What does prolactin do?
DELAYS metamorphosis
What effects does metamorphosis have in different tissues?
Different effects:
- Limb growth
- Tail degeneration
What causes cancer?
Loss of growth control
Where is cancer most common?
Why?
In tissues that continue to divide throughout life
85% epithelia
These cells are ALREADY PROLIFERATIVE - one step closer to getting out of control proliferation (each cell division = chance of copying errors)
What is a terotoma?
A tumour that looks like a disorganised embyro
How are the cells in a terotoma thought to be transformed?
Why?
By epigenetics (not permanently)
Cells can be transformed from the teratoma and transplanted into a normal area where they would develop
What are the PROTO ONCOGENES?
Ras
Raf
EGFR
Myc
What are the TUMOUR SUPRESSOR genes?
Rb p53 Ptc APC VHL
How can developmental signals cause cancer?
Play a part in self-renewal (eg. wnt, hh)
What cancer/s does activated Wnt cause?
Colon cancer
Hepatocellular cancer
What cancer/s does activated Hh cause?
BCC
Medulloblastoma
What cancer/s does activated Nodal cause?
Melanoma
What cancer/s does activated Notch cause?
Leukemia
What cancer/s does activated EGT cause?
Lung cancer
Breast cancer
