Class Notes (808,849)
Canada (493,411)
Biology (2,220)
BIO230H1 (243)
Lecture 4

Lecture 4 and 5 multicellular development T Harris.pdf

36 Pages
Unlock Document

University of Toronto St. George
Maurice Ringuette

Lecture 4 and 5 November 2, 201312:23 AM Talked aout how cells organize themselves structurally and spatially. Now we talk about how they develop. 1. Morphogenesis: the generation of tissue shapes which forms the whole body. 2. Cell differentiation: (next lecture) the generation of different cell morphogenesis types in different tissues. - we will be focusing on changes in gene expression in which they change behavior and identity. Morphogenesis involves a number of things Cell differentiation BIO230 Page 1 In early embryo there is cell proliferation so that you have enough cells to start working with Some of these cells becomes specialised, can also be viewed as differentiation because one cell ebcomes different from antoher, from another because of the different gene expression. They all have the same genomes but the expression is different. So the cell starts behaving differently from its siblings. It might feedback and afect proliferation: stop or increase cell proliferation. Affects how they move , the cell interaction, etc. then the cell can form different structures. this is morphogenesis. Additionally the cell specialization will also affect the function of the cell. You can create a muscle vs a neuron. They will look different and form different functions in the adult bodu It will change how they ineract with each other and it also affects how they move within the organism. Morphogensis is not exactly separate from one antoher. There is a wide number of model systems you can use to study the organims Gives the advantage of studying separate studies. Like high reproduction. One important aspect of this is that many of these are conserved among model systems. Nematode worm These developmental mechanisms are conserved across evolution. If you have a system which is conserved among these systems then that means that is important for development. There is a reason why its conserved and used again and again. Vertebrate models are close to humans and are closer models to human disesases. The close the model is to the us the closer we can apply them to human health. Fruit fly. BIO230 Page 2 Formation of the heart/ brain/ lungs can be thought of as having their own development processes. / autonomous from one another. Development processes keeps on happening in adults: They doesn’t stop in embryogenesis. Its key in adults for maintaining the tissues. 1. One is in the skin; the skin epithelium here: it’s a stratified epithelium. it is multilayered. Cells on top of cells. Beneath the stratified epithelium we have the extracellular matrix (connective tissue) and ECM molecules, and single cells migrating in that environment. Multiple layers provides protection from the Surrounding environment. The environment is harsh and the top layer of the skin cells are dead and it continually loses skin cells. Because we are losing skin cells we need stem cells from the base of the tissue which is resupplying the cells. If we don’t have the continuous resupply of cells we are losing the skin within two or three weeks. How quickly the skin cells are turning over. We have a new layer every two or three weeks, BIO230 Page 3 Another example: The lumen of the gut also has a very harsh environment. The cells exposed to this environment are also constantly lost. The epithelium right here is a single (monolayer) epithelium sheet which loops in and out forming a villi, Up the villi is the lumen of the gut. On the other side is the ECM. Typical arrangement of an epith. Sheet Right at the tip there are epithelium loosing. They are dying. So there should be resupply of them. Right at the base of the villi is the crypt. At the base of the crypt there is the individual group of cells which continually resupply tissues. These are the stem cells which are continually making tissues to resupply. If its stem cells are not there, You lose the lining of the gut in four weeks. In a woman when she became pregnant her mammary glands undergo new development processes. start with a simple epithelium. In preparation for feeding the infant the epithelium tissues buds off the alveoli . All the elvolie develops iff the tubes. the little circles. If we blow one of them up, its an individual epithelium monolayer. (simple epithlium, indivudla epithelium cells are shoen in pink, nuelci in darker pink/red) This sheet is going to pump milk into the lumen of the organ, then themilk is going to pass the aveolai and into the larger epithliu tube to feed the infant Example of apical basal polarity and trafficking within the cell. Individual cells are Making this milk fat droplets inside the cell, --> trafficked to the apical domain --> fed to the baby BIO230 Page 4 These developmental strategies are used again and again. In embryogenesis embryogenesis, organogenesis, stem cell development and also in adult development We start off with a simple ball of cells called blastocysts. We are looking at the mouse, the formation of the simple cells blastocysts. blastocyte The fertilized mouse egg, the haploid nucleus from the mother and the haploid nucleus from the sperm --> nuclei will fuse to make the diploid embryo-->the embryonic cell will divide a number of times --> there is a clump of loose cells at first. Then it will go through a process called compaction where the cells gain cell -cell adhesion to one another --> and then it gains compaction by cadherin molecules and cadherin is expressed which connects the cells to each other Then there is three main regions in the embryo --> an empty region in the middle called the blastocoel , the outer epithelium called trofactoerderm and inner cell mass : a group of cells in the outer epithelium sheet. This inner cell mass gives rise to the mouse/embryo, trophectoderm gives rise to the extra embryonic tissues which supports the growth of the embryo, like the placenta. From the fertilized cell you can make both the embryo and the supportive tissue. This inner cell mass then can make the mouse. This is the mouse. The inner cell mass is just a clump of cells and haven't turned into a mouse yet. BIO230 Page 5 The inner cell mass Is ONLY the embryo There are major things that have to happen to turn into the mouse. We know that there are types of cells outside and types of cells inside our body. So we need internalization of cells. Embryo is not a ball of cells, so elongation occurs. There are three topics we are going to talk, 1. Gastrulation: defines three main germ layers to the embryo a. Ectoderm b. Mesoderm c. endoderm Blastocysts: process of internalization of cells from blastocyst is called gastrulation. gastrulation Creates three germ layers: Ectoderm, endoderm, mesoderm. Ectoderm of the sea urchin: found outside of the embryo. Derives the Epidermis of the skin . The nervous system which is derived from the epidermis Endoderm: makes the digestive tract and organs which buds off the digestive tract Ecto is outside, endo is inside. In between it’s the mesoderm: gives rise to muscles, cells of the connective tissues, blood vessels. We walked in through the skin to the lumen of the gut in last lectures abdomen. Its similar in this too. You start off with the blastocysts which is a hollow ball--> this hollow ball is the entire embryo--> i(different from the mouse)if we flip back ectoderm one slide it looks like a hollow ball. So the hollow ball is coming from an inner cell mass which is coming from a more complicated way. Some mesoderm cells starts to detach from indivudla cells from the outer layer of cells and starts migrating inwards and start crawing inwards. The inward endoderm bending starts to make the digestiv etract and passes inway through BIO230 Page 6 Two main mechanisms to get cells inside the embryo: This is one mechanism, Where single cells separate from early outer epithelium. You can see the outer epithelium here apical Basal side will be facing the fibres, the connective tissue The other cells, Because they are not lined up perfectly in the Single cells separate epithelium, they are breaking off the individual cells and is appearing to Outer epithelium look as if they are migrating basal metastasise into secondary sites. Metastasis is extremely dangerous in cancer progression. If we understand the epithelium methucl..transition we can stop the this progression of cancer. During development this is highly regulated and the embryo controls which cell are allowed to undergo the local breakdown of tissues so cells can migrate away, and also controls where these cells are going to go in the embryo BIO230 Page 7 This is highlighted here: You can take a group of cells which you know is going through this transition. You can transplant them out of a quail and transplant them into a chick. We go from a quail to a chick because. you do this because these cells are not rejected by the chick because the organisms are closely related. But there are quial proteins which are not found in the chick, we can follow where do these cells go? Where do these unwanted cells go to? As the wing develops you can get a cross section of the wing and see that it specifically fomrs the muscle. Second mechanisms: Invagination Where the intact epithelial sheets moves inside the embryo No breakage, but only bending inwards Nice tall columnar individual cells/ all are rectangular from side view. Intact epithelium sheets At the apical domain, the actin and myosin that contract specifically at the apical domain. it makes the top of the cell to move in. instead of making a columnar it makes a triangle which initiates the internalization of the whole group of epithelium cells. (one triangle next to another triangle next to another triangle creates a bend) Happens in the formation of the neural tube - neurulation As the apical ends become narrower, Their upper surface membranes becomes thicker BIO230 Page 8 This drives the formation of the neural tube--> forming the spinal cord. In this it’s the ectoderm of the embryo. This is a frog embryo. Ectoderm is going through apical constriction and forms the neural tube --> tube is a cross section runs through the whole length of the embryo forming the spinal cord and the brain. Series of micrgraphs of the drosophila to make a moving animation These cells are marked with indiviudal nuclei. Apical constriction and inward bending of the tissue: cells are going to move inside the embryo --> detach--> and migrate around the nside. Example on how a sheet can move inside an embryo. In the last slide the cells were intact and didn’t move. This cells dissocaite and migrate around The ectoderm was talked about in the last slide. This slide mesoderm. So different organisms uses different strategies to internalize. Like in here. Not the same strategy for al tissues in all animals BIO230 Page 9 This is highly regulates, cells marks with a nuclei are told to internalize. Internalization is highly regulated by TF TWIST!. Cells that are marked by nuclei are marks so only these cells are internalized. This is done by TF TWIST. Cells that expresses the Twist moves into the interior of the embryo and forms the mesoderm. Others remains outside. BIO230 Page 10 Example of neural tube formation: Cross section of early frog embryo. The neural tube is forming. At the same time the neural tube is forming, the body of the embryo is elongating. Shifting from a walnut to In the end it looks like a tad pole How does it happen? Through specific cell rearrangement. The cells start to migrate to the midline (the green arrows). As they migrate in they push the neighbors to the head and tail. This leads to the extension of the body. So we have a convergent of cells to the midline and extension along the anterior posterior axis. This is a process called cell integration. Put your fingers togetherand The four fingers are contacting each other. You can see that its 4 rows of fingers high. Now indigiate youe fingers, so Fingers are moving towards the mid line os you now youhvae 8 rows fingers. This is regulated in the system so cells know where to go. Directionality : migration to the midline tells the cells where to go. BIO230 Page 11 We have a convergent of cells to the midline and extention along the anterior posterios access. This is called cell integration. Migration is regulated so cells know where to go. Another way to extend is by making more cells. Ex: Root hair of plants Root hair, They can extend very quickly, dive into the soil to look for water. That’s because they have a zone of cell division on the tip of the root. Upstream of this All the tissues are held together in the cell wall within the cell so it’s a static structure. And there is cell division at the tip. Only way the newly formed tissues can go is down. Preformed tissue is holding it back. Can't go up because of all the cell walls. By Having localized cell division you can force the growth downwards and force the extension of the tissue. There is also a zone of cell elongation as well as a zone of division. Cell sape change occurs there. This is how plants regulate their structure. They can orient their elongation but arranging the cellulose around their cells and also turgor pressure • Cell is divided --> elongated --> differentiated through the three zones at the root tip BIO230 Page 12 They can orient the elongation by orienting cellulose around the cells and also turgor pressure. Water is critical for plant structure if no water it flops over. Plant needs to be inflated by water. Now if you have cellulose fibres around a cell in a particular orientation then they can direct the direction of inflation. If you are holding a partially inflated balloon and inflate it, the direction of the balloon is dependent on the direction you hold it. B: the collagen fibres are holding back the extension of the cell in that direction so the only way the cells can expand is that direction. If you stack these cells on top of one another you are making a short plant. If you inflate a balloon the other way the balloon can go up or down. So in C, water can only push up or down effectively. So the cells stack on top on another forming a tall plant. Emphasize: Changes in cell division and shape are critical for animals development too. Ex: gut - The zone of dividing stem cells leads to a zone of rapidly dividing cells. Bsically you are have cell division happeing in one part of the cell and below it there is the ECM. Above it is the open lumen. So the Only place the cells can go is UP. They are forced to go up. Similar to the plant root. BIO230 Page 13 We need finer positioning of cells within the overall structure. One mechainsm is cell sorting. Cell sorting was recognized in frog embryo when the three germ layers were dissociated as single cells and mized back together. First: Mixture of cells randomly mixed together, Second: somehow can sort out from one another. There is some information in the cell which tells where and whom it should interact with. This provides finer information on where it should be in the embryo. BIO230 Page 14 There are three differential cell cell adhesion/ cadherin expression. We have different cadherin expression which is linked to cell sortin. We talked that cadhernid interacted homophilically. E cadherin interacts only with E . Vice versa. This is the homophilca bond between cells. The key idea: the fact that cadherin interacts homophillically. E with E. R with R. If you look at the brain, there are distinct zones in the brain which expresses e cahderin, r cadherin etc. Now there is attraction between the cadherins when you look at the brain you see that there are different zones in the cell which xpresses cadherin 6 , E and Z. When you look at the large zones of the brain we know there is a finer position in the brain. The brain is like a computer. How is its wiring setup? Cells are in different places of the cell.the larger structure is called the cell body. Where ever the nucleus is its called the cell body, out from the cell body there are extremely long extensions. there are axons and dendrites which wire up the body Cell bodies are in specific places and the cell extensions go to specific places in the brain. First look how the cells are positioned and then how the extensions are positioned. What it forms is the neural tube BIO230 Page 15 Formation of the brain: Forms from the neural tube. The formation if the neural tube is through invagination. We have a tube of Epithelial cells running from the top to the bottom. Top forms the brain. The bottom forms the spinal cord. Neural tube doesn’t have anything extended from it. Brain has to form more cells to make the neurons needed in the brain. Neurons start to divide. (progenitor cells for neurons) The daughters of the progenitor the cells associate with radio glial cells--> they crawl up the radial glial cells and occupy the zonal tissue of the radial glial-->. Then radial glial extends a little bit further --> when the next neurons are born -->. The next neurons walks even further out towards the extremities of the made --> so it continues. Making third, fourth layer of brain tissue. These are called radial glial cells. If we look at the brain, The radial glial are extendig in a radial orientation. Like spokes on a wheel. You start off with a cell like this and then walk to the first, second third layers. This is how the cerebra cortex the layers of the brain Is made of. This is how the cell bodies are made. Only the first step. We need to wire the cell now. If we know that these wirings have to go from cell body to cell body. Where should the wirings be. The axon is doing all the migrations using a specific structure called growth corn which is at the tip. This growth corn moves via actin based protrusions. The growth cone is like the immune cell that was chasing the bacterium( you can think like that). Same process as the front of the growth cone. it can move and push the cell forward. Difference is that the immune cell moves the whole body. But in this the cell body stays in place so instead you have a long extension in between. This is extremely precise and can be reproduced In the body BIO230 Page 16 You can get a dye and observe the zone of projections from one part of the brain. From the eye to the brain. Get a tadpole and inject one dye and can see the axon going from one part of the brain to the opposite side. Somehow the neurons knows how to migrate from the brain to the eye. There are so many neurons its complicated to understand the path. There are so many neurons are made. So instead of looking at the process at the brain, we can look at the process further down the neural tube and ask the behavior of neurons down the neural tube. Below slide. Dyes go to opposite sides. You can look at the procedure further down the neural tube and ask the behavior of neuraons down the neural tube. From the neural tube to the brain. You can look at the axon path finding from the neural tube to the brain. Basically around the neural tube Neurons been born all through out the tissuse . Then they send axons ,first down to the midline of the floor plate. That means one side of the tube, they all send axons to one side of the tube and they all migrate it towards the brain. All the axons forming the spinal cord are going to go towards the brain. This is the growth corn at the tip of the cell so it has to make a couple of decision. At first has it to find the midline --> then the brain. It is not complicated as in the brain, but still reamarkable. BIO230 Page 17 This is the tip of the axon. We are looking at the growth cone here. Right along the mid line, center of the tube, of the group the first step is attraction to the midline --> occurs through a process similar to the immune cell chasing after the bacterium Attractant is secretes a protein along the midline and forms a gradient( like the bacterium secreting small moelcule) --> cell receives the signal---> recognizes gradient -->orients the actin protrusion machinery in the midline --> migrates ti the midline Just like in the immune cell Diffence is that if the immune cell captures the bacterium and its job is done. But in this the growth corn has to turn and migrate to the brain after it reaches the first step. How does that happen?
More Less

Related notes for BIO230H1

Log In


Don't have an account?

Join OneClass

Access over 10 million pages of study
documents for 1.3 million courses.

Sign up

Join to view


By registering, I agree to the Terms and Privacy Policies
Already have an account?
Just a few more details

So we can recommend you notes for your school.

Reset Password

Please enter below the email address you registered with and we will send you a link to reset your password.

Add your courses

Get notes from the top students in your class.