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Lecture 6

Lecture 6 - morphogenesis.pdf

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University of Toronto St. George
Maurice Ringuette

Lecture 6 November 5, 20110:41 AM We talked about how adult structures can develop. Now we talk about how its maintained. All structures need maintenace. Once cells in tissues are born they continuously regenerate. Can happen in 2 level.s Moelcular turnover: cells stay intact and molecules in the cells turn over. Cellular tunroner: cells dies and maintain the overall tissue structure The reason that these tissues are maintained themselves for a lifetime because tehey have a very specific architectutre and function. turns into neuro impulses.real speicifc architecture to detect photons and convert them into neural impulses the brain and we all can see. The brain can convert it to images we can see. There is a structure of the cell which has outer and inner segmens. The disk of photoreceptor membranes where photons are detected. This leads to the change in thec ell --> activation of the synaptic regions so the single can be sent to the brain. If you look at the overall retina, the photoreceptors are ar ewat the back of the retins so the light coming it towards the eye tp the retina, the receptor cells are in the nack, the neurins and azons are in front of the receptors . Lights hit the photoreceptors --> hits the neurons --> sends signal.this is a specail architecture in animals. Are the molecule truning over. The question is are the molecules turning vier or permant. BIO230 Page 4 You can use the pulse chhase to look at moelcaular tunrover. You add a smal amount pf pulse for a small amount of time and stop adding it and watch what happens to is, follow it. Here the radiolabeled Leucine: AA.we are labelling all the proteins. Cells will take up the labelled leucine: ncorpaotaing them to the newly synthesized protiens in a short period if time. 1. They are going to be detected in the cells for an entire life time. Which means that the same proteins that are been made which took that protein stays in the cell for the rest of the life time of that cell. 2. Or its gradually loses the detection indicating Moelcular turnover. 1. Time point one: Shortly after leucine was added. The labelled proteins are found in the nucleus. Where the proteins are made and labelled. Fter the pulse of the other leucines are been made. 2. The proteins are made in the nucleus. So there are other leucines which are been made and they move up into the mmebranes and then they differ into the pigmented epithelium cells. They keep on shifting up and insert the pigmented epithelium in the photorecptors. One thing is that there isa flow of molecules…there are constant flow of unlbaleled molecules which goes in the cell too. It is been followed by unlabeled molecules. There is a flux of runnnig fliuisd, while cell is intact. The pigmneted epithelium cell is eating the top of the photorecptor cell. It’s a phagocytic cells, Its biting off the membrane, indgesting and degrading them. there is constant synthesis of material by the biosntheric pathway. Or the cell would grow right? Example of tunroveR in our bodies: Bones are continually turned over. This is an extracellular example. We continually have cells called osteoclasts which are eating and emlininating our bones. You have cells called osteoblasts. They eat our bones and eliminate them. The image is a extracellular matric molecules, packed version. Ver cells, just polymers. There are the osteoclasts moving away, whie eatng. secreted acids and digestive acids had broken down and destroys the bone. We have another type called the osteobalsts which continue to secrete the bone. The balance between the two is critical for the bone structure. Osteoprosis is the imbalance between osteoclasts and osteoblasts. Too much bone destruction and not enough reuilding of bones BIO230 Page 5 Now lets look at cellular turnover. This can be stem cell dependent or stem cell independent. When we decide if its stem cell dependent or independent we need to know the definitoin of stem cel. Stem cell : is not differnetiated. In previous elctures we saw the begninning cells where genes were asked to turn on or off. Stem cells don’t do that. They are not differntiated. They can divide unlimitedly. Their dayghters can remain a stem cell or they can differentiatte. Stem cells don’t tell to turn on / off genes. It stays in the same exact state it was. The Terminally differentiatied daughters either remain as stem cells or they Without limit differentiate. This differentiation is the same kind of choice we taling eabout in the fdevelopment of embryp This is breaking the rule of stem cell: because it happen from stem cell differntaition. This can occur in the liver. If you cut the liver in half it will grow until it regrow the size where the cells need to. Oancreas; diffentiated cells renewig the tissue. There should e specific mechanisms for the stem cells to work in the life time of the animals. BIO230 Page 6 The fate of stem cell daughters have to be controlled. This can be controlled in two ways, to both maintain the stem cell population and to control how the other daughters diffentiate. You can see from the examples that the concepts are identical to what we saw in th e differentiation lecture in embryogenesis. One case is divisional asymetry.: Intrisic mechanims prmotng cell Can’t be restored differntiatinn. Red factors promite asymetric cell differntiation. The one that doesn’t recive that factor differentiate. If the stem cells are lost the original members cannot be stem cell makes one stem cell. If you have 100 stem cells, you get 100s stem cell. If you break this by 50 then you get 50 stem cells. That’s the concern about the mechanism, you can lose the population and its difficult to restore. Second mechanism: Identical to the extrinsic cue. Daughters are born the same, but born into different environments. Cell divison is symettric and Fate is determined about the environment. The nice thing about the mechanism is if stem cells are lost, their numbers can be increased by both daughters entering division by promting stemness. If you have two many stem cells let both daghtersgo into the envirnoement to diffentiate. So there is regulation possible in this system BIO230 Page 7 If the stem cells were to last an entire life time of the organisms, you can imagine if we were born with a certain number of stem cells,how does it last an entire lifetime? Cell divisions have problems with them. there are mutations associated with the division of cells. Packing and moving of the dna leads to muations. Every time a cell divides it gains mutations. Everytmie the cell divides telomeres gets depleted. If the cell divides too much it gains mutations. Its chromsomes are getting unstable because of the loss of telomeres. So cells overcome this by dividing slowly. So it divides only a couple of times during the life time. It divides much more slowly. So then how do we make enough cells to make a tissue of the stem cells divide slowly? There is a cell type stage which is called the transit amplifying cell. This occurs just as soon as the stem cell has divided. We can see the stem cells has renewed itself. And the other daughter has gone to differntiate Before it diffenrtiatie ts it starts to divide like crazy. This is where it catches up it can divide rapidly. It doenst matter if it divides lot. Because it is differntiaite. Okay for I tot gains mutaions because it is already diffenttiated and will bne perfomrin tht enoirmal functions of the tissue. This ica resuppy the tissue and maintain the tissue structure. BIO230 Page 8 Third concept: stem cell Niche: specific environment that helps promote the stem cell character. It will supply the signals which will promote stemness and maintain the stem cell population. A nice example is the skin stem cells which reside in the basal layer and require attachment to the basal lamina to remain a stem cell. Balsal lamina provides the niche. Picture: The base of the skin: This epithelium layer is unique and its stratified. That means have multiple cell layers in the epithelium. The base is in contact with the ECM like any other epithelium. The basal lamina is just a sheet of extracellular material.not cellular material but its extracellular fibre
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