Normal control of cell growth and differentiation Flashcards
Morphogenesis
Shape organism by embryological processes (differentiation and growth)
Undifferentiated cells can…
Differentiate, apoptosis, proliferate, grow
Most common in early development = proliferation + growth (usually coupled)
Cell growth requires…
- Increase cell mass and volume - macromolecule synthesis (polysaccharides, proteins, lipids)
- Relative movement at cell surface - change interactions/ connections w/ other cells and ECM
- Change shape
Why is cell growth important?
- Massive but consistent size increase during development
- Huge diff. animal sizes (even though same mechanisms regulate)
- Organs maintain in proportion to each other
- Cells in many organs cont. grow during adulthood
- Defective growth = disease (esp. cancer)
Cell growth and survival influenced by…
- Extracellular growth factors and inhibitors
- Contact w/ extracellular matrix
- Normal growth cond. = organs grow to fixed size (intrinsic control of growth)
- Regulate growth - reduce/ xs extrinsic growth factors
- Nutrition
When does cell growth occur?
Early development: Fertilised egg - embryo - fetus - adult
Huge increase in size
Adult: Hypertrophy (growth, no division) - e.g. skeletal muscle
Hyperplasia (coupled growth and proliferation) - renew tissues (stem cells)
Disease: Neoplasia - tumour growth (abnormal growth and division)
Hypoplasia
Cell/tissue loss
Development: Tissue patterning - digit formation, neural patterning (many neurons formed during development die)
Physiological atrophy (decrease size) : Pulmonary artery/ aorta at birth, thymus at puberty, epithelial cells
Developmental/ physiological disorders: Hypoplasia and atrophy - testes in Klinefelter’s syndrome, skeletal muscle degeneration after denervation,
neurodegenerative disease of ageing
Coupling of cell growth and proliferation
Current model = growth drives mitosis
Uncoupling of cell growth and proliferation
Proliferation w/ no growth - cleavage
Growth w/ no proliferation -skeletal muscle hypertrophy
Growth w/ DNA replication but no division = big cells ( e.g. myocardial cells - skeletal muscle fibres fuse)
How is normal tissue structure and function maintained?
Cell growth/division
Control - extracellular growth factors/ inhibitors
Balance by cell loss/death
Growth factors
Local factors - control growth of specific organs
Global factors - regulate coordinated growth of multiple organs (e.g. nutrient dependent)
How is organ size regulated?(experimental)
Autonomous control:
Transplantation experiments
Organ size usually determined autonomously
Transplant multiple fetal thymuses into developing mouse
Each grow to adult size
BUT transplant fetal spleens
Total mass of spleens = mass of normal spleen
NON-AUTONOMOUS control
Regeneration experiments
Hepatocytes regenerate ⅔ liver
Observe role of growth inhibitors
Non-autonomous control:
Defects in growth regulatory pathways
Reduced/ XS GH
Insulin receptor mutant (leprechaunism in humans)
Drosophila insulin receptor signalling - control body growth and affects lifespan
Link to nutrition (birth weight, health, lifespan) - Expression and activation of regulatory pathways
Signals from neighbouring structures - Sympathetic neurons and nerve growth factor
Renewing tissues: skin
Stratified squamous keratinised epithelium layer, basal layer contains proliferating SCs, cells move through layers, sloughed off at surface, move through states of gene expression towards terminal differentiation
Cells express series diff. keratin proteins during differentiation
30 day process - cell divide to slough off at surface
Basal layer contain few true SC (TSC) but many transit amplifying cells (TAC)
TSC not divide often - limit potent. mutations
TAC - potent. rapid repopulation when need (wound repair)
Move to skin surface
Renewing tissues: gut
Lining s.intestine renews faster than other tissues (1 week turnover)
Dividing multipotent stem cells in crypts, travel upwards to villus tip
Cells undergo apoptosis
Shed into gut lumen
Paneth cells migrate down
Regulate by cell-cell signalling
Produce 4 type differentiated cell
Resting tissues: liver
Survive surgical removal 75% total liver mass, original no. cells restored in 1 week, original tissue mass in 2-3 weeks
Hepatocytes
High capacity for cell division
Unipotent stem cell
Most tissue repair in liver
Also liver stem diff. from hepatocytes - respond to some forms x liver injury
Oval cells = hepatocyte precursors