Lecture 8 - Growth Flashcards
Why must tissue growth be regulated?
To maintain the correct proportions to drive morphogenesis
What are the 3 types of tissue growth?
- cell proliferation
- cell enlargement (cellular hypertrophy)
- growth by accretion - cells can be instructed to produce more extracellular matrix
What are the 4 stages of the cell cycle
- M phase
- G1
- S phase
- G2
In what stage of the cell cycle is the cell in most of the time?
G1 - making material (transcribing genes)
What is the purpose of checkpoints in the cell cycle?
to make sure everything is in order before mitosis & cytokinesis
Why are checkpoint genes often mutated in tumours?
to allow cell proliferation
What molecule can be found at the start checkpoint (between G1 & S)?
FGF
Why is tissue regulation important in setting the adult growth size?
different cell tissues grow at different rates. As a result, growth rate is carefully regulated
What 3 signals control body size?
IGF - insulin-like growth factor
GH - growth hormone
GHRH - growth hormone-releasing hormone
Where is growth hormone made?
pituitary
Where is GHRH (growth hormone releasing hormone) kept?
deep in brain in hypothalamus
Describe what occurs when there is too much Growth Hormone present?
Too much GH - increase in somatostatin (secreted from hypothalamus) - leading to inhibition of GH production.
Describe what occurs when there is a lack of Growth Hormone present?
Low levels of GH - stimulates GHRH from hypothalamus, leading to the upregulation of GH
How does GH actually regulate tissue growth?
Regulates production of IGF1 in the liver & bone.
Where is GH found?
found in circulation - as is IGF1
What produces IGF1?
Liver is the main producer - bone also produces it locally.
What is genetic ablation?
the production of toxin or destruction of components to regulate an organisms size - carried out by themselves
What are the 2 pathways to regulate organ size?
TOR pathway
Hippo pathway
How does the TOR pathway regulate organ size?
increase in cell size
How does the Hippo pathway regulate organ size?
Reduces cell size by blocking cell proliferation & by inducing cellular death.
What can occur if there’s a mutation in the Hippo pathway?
can cause organ hypertrophy - due to increased proliferation
What is apoptosis?
Deliberate suicide if an unneeded cell. This involves the careful coordination of the shut down cell - followed by engulfment of the remnants by other cells. Apoptosis is caused by stress. In adult tissue it is used for homeostasis (e.g. mammary glands) & health (e.g. get rid of infected (viral) or genetically compromised (tumour) cells.
What is necrosis?
can be caused by injury, infection, cancer, infarction and inflammation.
- disorderly, dying-off of cells without any signal to or from the neighbouring cells
- cells just split open & empty their contents into the surrounding tissue
How does muscle growth regulate itself?
Myostatin (signaling molecule) is secreted by muscle fibres. It provides negative feedback on muscle growth.
How does mutations affecting myostatin activity affect muscle mass?
It increases muscle mass
How does myostatin regulate muscle growth?
- It reduces myoblast proliferation (through Rb)
- It reduces muscle differentiation (through MyoD)
What occurs if there is a removal of part of the kidney?
there will be an increase in the size of the remaining kidney
Why does the remaining kidney grow if a part has been removed?
in response to a rise in the concentration of creatinine in circulation
What is creatinine?
a waste product which signals the need to increase kidney function - an increase can be due to cell enlargement
What produces and regulates bile acid levels?
liver
How can you artificially cause the liver to grow?
artificially increasing bile acid in circulation, which leads to cell proliferation. This will eventually lead to bile levels reducing due to liver absorption.
What drives body growth as a whole?
skeletal growth
What does the skeleton form from?
cartilage in the embryo
What is the process by which the cartilage template turns to bone?
ossification
What is a chondrocyte?
cartilage cell
What is an osteoblast?
bone cell
Where does cartilage reside after ossification?
cartilage remains in the joint areas
What colour does the bone matrix go when treated with Alizarin Red?
red
What colour does the cartilage matrix go when treated with Alician Blue?
Blue
What drives postnatal growth in long bones?
chondrocytes
What are growth plates made of?
proliferating chondrocytes
What happens to growth plates at the end of puberty?
they close
What is found where the cartilage meets the bone?
growth plate
What 3 events occur in the cell plate?
- cell division
- hypertrophy
- apoptosis (chondrocytes) & ossification
What does high levels of androgens (e.g. testosterone) in the ring finger in the embryo lead to?
Promotes growth
What does high levels of estrogens (e.g. testosterone) in the ring finger in the embryo lead to?
Repressed growth
