L7 - Growth and Cancer Flashcards
What must occur before growth can occur
Patterning over a small scale
How does differential growth account for differences in the limb in bats and humans
Have the same humerus - radius/ulna - digits
But in bats these are elongated to a much greater degree
3 methods of growth
Cell proliferation
Cell enlargement
Accretion
Cell proliferation AKA
Hyperplasia
Cell enlargement AKA
Hypertrophy
What drives G1 phase
Cdk4/6 and cyclin D
What drives G1/S
Cdk2 and cyclin E
What drives S/G2
Cdk2 and cyclin A
What phase of the cell cycle do terminally differnetiated cells enter
Quiescent
Early drosophila embryo is a
Synctiium (single multinucleate cell)
Describe the cell cycle in the early divisions of the drosophila embryo
Rapid synchronous cycles of only S and M phases
Describe what is seen at the 14th cycle
Slowing of the cycle and introduction of G2 phase
What is the division rate in the drosophila embryo determined by
Location of that cell
Groups of cells with similar fates may have similar division rates - what is term used to describe this
Mitotic domains
Cell division in mitotic domains is controlled by what protein
String
During the first 13 division describe the distribution of string
Uniformly distributed owing to its maternal origins
This allows for the rapid synchronous divisions
Describe the distripution of string after the first 13 division
Zygotically expressed string produced under the direct control of the patterning genes
What happens in the mesoderm to string and why?
Tribble blocks string
Mesoderm must first involute before any growth can occur
Describe what would happen if there was an additional thymus gland - what ype of control is this
All organs maintain their size and multiple ammounts of tissue will be present
INTRINSIC CONTROL
Describe what would happen if there was an additional spleen - what type of control is this
Both would grow to half the size such that the total ammount of spleen tissue remains the same
SYSTEMIC CONTROL
What pathway controls the size of the cell
TOR pathway
What pathway limits the size of organs
Hippo pathway
Describe the hippo pathway when it is inactive
TF Yki/Yap/Taz is in the nucleus which stimulates growth and promotes the survival of cells
Describe the hippo pathway when it is active
Transcritpion factor Yki/Yap/Taz excluded from the nucleus and growth is inhibited
What factors lead to the activation of the hippo pathway
What is the result of this activation
Cell cell contact
Cell polarisation
Activation of pathway leads to inhibition of grwoth
What factors lead to the inactivation of the hippo pathway
Mechanical stress - because there are not enough cells so this causes some cells to become streched
Other signalling pathways
Describe a hippo mutant version of the fly imaginal disc
Mutant disc much bigger in size
Yki is in the nucelus
Ability to restrict growth has been lost
Describe a hippo mutant liver
Mutant much bigger
Yap/Taz in the nucleus
Ability to restrict growth of cells has been lost
Name an example of a area where growth rate is not unifrom
Head
Why are pygmess shorter
Second growth spurt doesnt happen
Size of the adult fly determined by
Size of the larva
What affects duration and rate of fly larval growth
Insulin
When the larva reaches a certain size what occurs
Metamorphosis
What induces metamorphosis in the fly
Edcyson
What are the main determinants in the difference in size of dogs
IGF and GH pathways
What hormones control growth in mammals
GF1 GF2 IGF1 IGF2
Production of growth hormone in the pituritry activated by
GHRH (growth hormone releasing hormone)
Somatostatin
What is the main site for IGF production
Liver
What an example of how maternal environment can affect growth
Shetland cross shire horse
If mother is the Shetland then the foal is smaller
Compare the signals used for development and then during post embryonic development
Dev - short range and small
Post emb dev - influences from the environment act on the CNS which then produces hormones which act at the scale of the whole organism
Molting is AKA
Ecdysis
Why must motling occur
Since cuticle is rigid and doesnt allow for much growth to occur
Intermolds are refereed to as
Instars
Molting initiated by
Activtion of strech receptors in the cuticle
Once strech receptors have been activated what occurs next
Release of protothoracicotrophic hormone from the corpus alatum
Release of protothoracicotrophic hormone leads to _________________________
This leads to
Ecdyson from the prothoracic gland
Molting then occurs under influecne of ecdyson
Describe the process of molting
First cuticle separates from the epidermis
While original cuticle is still present freed epidermal cells prolfierate and secrete a fluid forming a barrier which begins then secreting a new cuticle - only after this will the old cuticle be shead
What prevents metomorphosis in flies
Ecydyson
What causes ecdyson release - where is it released from
Brain releases prothoracicotrophic hormone which then acts on the prothoracic gland causes the release of ecdyson
Describe how metamorphosis is triggered in frogs
Hypthalmus releases CRH
acts of the pituitrary to release of TSH
Causes the thyroid to release thyroxin (T3 T4)
What delays metamorphosis in frogs
Prolactin
Cancer is essentially the
Loss of growth control
Where is cancer most common
In already proliferating cells - such as epithelia
What are teratomas
Cancer cells which give rise to tissues of all 3 germ layers
Protooncogenes
Once activated become oncogenes
Genes that can cause cell division
Ras Raf EGFR Myc
Tumour supressior genes
Once inactive cause cancer
Usually decrease the rate of cell division
E.g. Rb, P53, ptc, APC, VHL
Type of cancer caused by abberent Wnt
Colon cancer
Hepatocellular cancer
Type of cancer caused by abberent Hh
BCC
Medulloblastoma
Type of cancer caused by abberent Nodal
Melanoma
Type of cancer caused by abberent Notch
Leukaemia
Type of cancer caused by abberent EGF
Lung cancer
Breast cancer
Describe dominantly inherited cancer syndromes
TSGS at the centre
Two hit hypothesis
If inherit a faulty copy of the gene
Easier then for the remianing copy to become damaged
