growth Flashcards
what must tissue growth be
-differentially regulated to maintain the correct proportions and to drive morphogenesis
what are the Different types of tissue growth
-cell proliferation- involves cell division, 2 daughter cells are halve the volume of mother cells- have to go through hypertrophy to get to the mothers size
-cell enlargment- hypertrophy
-growth by accretion- secrete EC matrix (proteins etc.) I increases size of tissue e.g. cartilage
4 stages of cell cycle
-M phase- mitosis and cytokinesis
-G1
-S (DNA rep)
-G2
-G = gap phase (pause)
-G1 can be very long or permanent
Most cells in the adult are in G1
-S, G2 and M are irreversible and the cell must proceed on to G1
what are the different checkpoints of the cell cycle and why do we have them
-ensures that a cell does not enter mitosis unless needed
-The Start checkpoint is the important checkpoint for development.
- G2 and metaphase to anaphase checkpoint - These check points have to do with making sure everything is in order before mitosis and cytokinesis (cell division).
-Check point genes are often mutated in tumours to enable cell proliferation (eg retinoblastoma, Rb)
-Rb inhibits entrance of cell cycle and FGF and IGF activates it
whats the most important hormone
-growth hormone
whats body size centrally controlled by
-hormones
-Hormones are signalling molecules that are circulated around the body
-GH is a central regulator that acts primarily on the skeleton to cause an increase in size.
-Three negative feedback loops
-These interactions must be balanced
-IGF: insulin-like growth factor
-GH: growth hormone
-GHRH: growth hormone-releasing hormone
hypothalamus and growth
-GHRH activates GH -> local IGF-1 -> bone
-GH inhibits GHRH
-somatostatin inhibits GH -> liver -> IGF-1 synthesis -> circulating IGF-1 -> bone
how do Organs have ways of measuring their own size
-A transgenic mouse is generated that expresses diphtheria toxin under the control of tetracycline.
-This type of experiment is called a genetic ablation.
-pancreas: tetracycline-mediated ablation to E10.5
-liver: tetracycline-mediated ablation to E13.5
what occurs in the Regulation of organ size by TOR and Hippo pathways
- Tor pathways: cell growth -> increased cell size -> organ and body size homeostasis
-hippo pathways :
1)activation of cell death-> inhibits cell number -> organ and body size homeostasis
2) inhibition of cell proliferation -> activates cell numbers - > organ and body size homestasis
whats apoptosis
– Apoptosis is the deliberate suicide of an unneeded cell.
- It involves careful coordination of the shut down of the cell – followed by engulfment of the remnants by other cells.
-Apoptosis is caused by stress such as starvation or excessive DNA damage.
-It is used during development to cull unneeded cells.
-In adult tissues it is used for homeostasis (eg mammary gland) and health (eg to get rid of infected (viral) or genetically compromised (tumour) cells).
whats Tissue-specific regulation
-Myostatin is secreted by muscle. It provides negative feedback on muscle growth. Mutations that affect Myostatin activity cause increased muscle mass.
-It reduces myoblast proliferation (thru Rb) and muscle differentiation (thru MyoD).
-myostatin activatesRb which inhibits proliferation
-myostatin inhibits MoD which activates the conversion of myoblasts to multinucleate myotube -> muscle fibre
-mesodermal progenitor -> myoblasts -> multinucleate myotube -> muscle fibre which activates myostatin
whats necrosis
Necrosis can be caused by injury, infection, cancer, infarction, and inflammation. It is the disorderly, dying-off of cells without any signal to or from the neighbouring cells. Cells just split open and empty their contents into the surrounding tissue.
whats the Functional regulation of organ size (adult)
-Removal of a kidney leads to an increase in size of the remaining kidney, perhaps in response to a rise in the concentration of creatinine in circulation. Creatine is a waste product which signals the need to increase kidney function. The increase is primarily the result of cell enlargement.
-The liver produces and regulates bile acid levels. Artificially increasing bile acid in circulation causes the liver to grow in response. The increase is the result of cell proliferation. This leads to bile levels being reduced by liver absorption.
what does most skeleton form as
-cartilage template in the embryo
-Chondrocytes secrete cartilage matrix in the shape of the skeleton.
-Over time bone is formed on the cartilage matrix by osteoblasts (ossification)
-During ossification the chondrocytes die by apoptosis
-Cartilage remains in the joint areas in adults
-mouse embryos: Bone matrix is red when treated with Alizarin Red
Cartilage matrix is blue when treated with Alcian Blue
chondrocyte = cartilage cell
-osteoblast = bone cell
what do chondrocytes drive in long bones
-postnatal growth
-Growth plates contain chondrocytes that proliferate, hypertrophy and then die. The remaining cartilage matrix is turned to bone by osteoblasts.
-resting -> cell division -> hypertrophy -> apoptosis and ossification
what is a Sex specific differences
-right hand
-female: index finger is longer
-male: ring finger is longer
-In the embryo:
=High levels of androgens in the ring finger (4D) promote growth
=High levels of estrogens in the ring finger (4D) repress growth
