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
-
Introduction0
-
Gastrulation/germ cells60
-
Adult stem cells66
-
In vitro stem cell models70
-
Gut organoids30
-
Aging and senescence64
-
Regeneration75
-
Post embryonic development66
-
Cancer and stem cells60
-
The cell cycle I79
-
The cell cycle II41
-
Oncogenes54
-
TSG64
-
Checkpoint controls I52
-
Checkpoint controls II42
