Growth Flashcards
Different types tissue growth
Cell growth must be differentially regulated to maintain correct proportions and to drive morphogenesis
Different types tissue growth:
- Cell proliferation (production of daughter cells)
- Cell enlargement
- Growth by accretion
- Cell hypertrophy - makes cells bigger
Cell proliferation
Rates division must be carefully regulated to maintain cell numbers in given tissue
After early development division is slower, typically one division every 24hrs in proliferating mammalian cells
Other cells don’t divide once born and lost for many years
During DNA replication each chromosome (maternal and paternal) is duplicated to give rise to sister chromatids
Sister chromatids must be distributed (segregated) into daughter cells
The cell cycle has 4 stages
G = gap phase
G1 can be very long or permanent
S
G2
M
Cell cycle has different checkpoints to ensure that cell doesn’t enter mitosis unless needed
S, G2 and M irreversible and cell must proceed onto G1
Start is important checkpoint in development, influenced by nutrition as cell needs it to be favourable to begin
The G2/M checkpoint and the Metaphase-to-anaphase transition checkpoint have to do with making sure everything is in order before mitosis and cytokinesis
Rb is main inhibitor as start checkpoint (is at almost the end of G1) to make cell stay in G1
Checkpoint genes often mutated in tumours to enable cell proliferation (e.g. retinoblastoma, Rb)
Overall growth is important in setting the adult size
All controlled by hormones from pituitary (makes hormones signals throughout whole body to promote growth) and hypothalamus
Body size is centrally controlled by hormones (need to update once I’ve gone back over lecture)
There are 3 negative feedback loops that control body size
These interactions must be balanced
IGF: insulin-like growth factor
GH: growth hormone
GHRG: growth hormone-releasing hormone
When things start to growth they send signal back so pituitary and hypothalamus then know that its received signal to grow and so will stop sending so much growth hormone as you don’t want to over grow
Organs have ways of measuring their own size
A strain of mice generated that carries an introduced gene for diphtheria toxin under control of tetracycline-repressible promoter
A transgenic mouse is generated that expresses diphtheria toxin in tissue of interest when tetracycline is administered
This type experiment called genetic ablation
tetracycline responsive transcription factor known as an inducible promoter
When administered to pancreases and liver of mice it caused them to shrink with the pancreas weighing 36% of normal in embryo and 40-50% normal in adult and in liver weighing 33% of normal in embryo and 86% of normal in adult
Regulation of organ size by TOR and Hippo pathways
Mutations in hippo cause organ hypertrophy as it doesn’t cause cell death
TOR pathway grows cell size
Hippo pathway inhibits proliferation and signals for cell death
Apoptosis
Is the deliberate suicide of unwanted cells
It involves careful coordination of shut down of cells, followed by engulfment of remnants by other cells
Apoptosis caused intrinsically by stress such as starvation or excess DNA damage
Is used during development to cull unneeded cells
In adult tissues is used for homeostasis (liver and mammary gland) and health (e.g. to get rid of infected (viral) or genetically compromised (tumour) cells) and in immune system ensure self reactive cells remvoed
Necrosis
Can be caused by injury, infection, cancer, infarction and inflammation
Is the disorderly, dying-off of cells without any signal to or from neighbouring cells
Cells just split open and empty contents into surrounding tissue
Tissue-specific regulation
Myostatin secreted by muscle, provides negative feedback on muscle growth
Mutations that affect myostatin activity cause increased muscle mass
It reduces myoblast proliferation and muscle differentiation
Myostatin activates Rb which blocks mitosis
Myostatin blocks MyoD which helps muscle differentiation, leads to you getting lots of undifferentiated muscle
Functional regulation of organ size
Removal of kidney leads to increase size of remaining kidney
Perhaps response to temporary rise in concentration of creatinine in circulation, which signals need to increase kidney function, the increase result of cell enlargement
Liver produces and regulates bile acid levels, artificially increasing bile acid in circulation causes liver to grow in response, increase is result of cell proliferation, this leads to bile levels being reduced by liver absorption
Skeletal growth drives body growth
Most of the skeleton is formed as a cartilage template in embryo
Over time bone formed on cartilage template
Chondrocyte = cartilage cell
Osteoblast = bone cell
Cartilage remains in joint areas
In mouse embryos did experiment where bone matrix is red when treated with Alizarin Red cartilage matrix is blue when treated with Alcian blue, allows to see images of bones forming
In long bones chondrocyte proliferation drives postnatal growth
Growth plates made up of proliferating chondrocytes
Growth plates close at end of puberty
Cell division leads to hypertrophy in growth plates
The hypertrophy then also leads to apoptosis and ossification
Sex specific differences
In embryo:
- High levels of androgens in right finger (4D) promotes growth
- High levels of oestrogens in ring finger (4d) repress growth
So would expect ring finger to be shorter than index in female and ring to be longer than index in male
