MCDB 423 Lecture 16: Lecture 16

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Molecular, Cellular and Developmental Biology
MCDB 423
John Kuwada

Lecture 16 Slide 2 We need our brain to process spatial information via touch, hearing and vision Our brain has topographic maps where spatial information we’re getting is mapped physically The cartoon shows an example of a topographic map of the visual system -Retina gets spatial information -One part of the retina, the cells are receiving different information from another part of the retina The retina sends a long axon to the midbrain (in the case of frogs, it’s called a tectum) Slide 3 Manipulate the relationship of the retina ganglion cells to the midbrain We can change the relationship by taking out the eye and then inverting it a 180 degrees and then let the neurons connect to the brain -So can it make a functional visual system when the eye is inverted? What they found was that the frog responds to a stimulus in an inverted way -So spatial information is retained in the midbrain but it is inverted If you look molecularly at the axons, they are still going to their specified place in the midbrain even though their position in the retina changed This is called the chemospecifity hypothesis -It says that there is some information in the developing brain that tells those axons to go to a specific place -We know now that there are molecules that cause this slide 4 The blue are growing neurons that are extending their axons -Neurons make axons after they are differentiated -There are molecules that are guiding the direction of growth slide 5 This is an image of a single retinal ganglion cell There are multiple cues and choice points that the axon makes along the way Today’s lecture will be about these cues and receptors Monday will be about the growth cone (part of the axon that is sensing the signals and doing most of the work) Slide 7 In this stage, we can see that they are growing in a very specific directions Growth cone is a dynamic chemosensing structure Slide 8 There are many molecules that play a role in guiding Don’t have to memorize all of them Some of the molecules are secreted proteins so they can hang out in the extracellular space and be present for growing axons to see Some have a transmembrane domain so that they are presented on the cell -So the axons would have to physically touch these cells Receptors have intracellular domains which can cause a signal cascade that allows the cell to sense that the ligand is present -These receptors would be on the growth cone of the developing axon to sense the information slide 9 These are some of the examples of the cues we can see for a growing axon The extracellular matrix has molecules that are growth promoting for developing neurons so contact with molecules in the extracellular matrix can help a neuron to grow it’s axon in a positive way Molecules on the surface of the cell can be growth promoting or repulsion Slide 10 For extracellular matrix adhesion, growing axons can detect differences based on what you present it on the dish Slide 11 Molecular example of this Molecules such as laminin in the extracellular matrix can bind to neurons called integrins which have no transmembrane domain and they link ultimately with the cytoskeleton actin -Makes adhesion for the neurons to stick and grow slide 12 These can be mediated by a huge class of molecules called CAMs -These molecules are expressed on the surface -Allows cells to stick to one another You can have two cells expressing the same molecule -That molecule makes a dimer Or you can have specific pairs of interaction that specifies a specific interaction There are also cadherins which are homeophilic which are Ca+2 regulated (blue in the image) -So they need Ca to bind slide 13 Answer = c Cadherins have a Ca binding domain so in the Ca bound state, they can homeophillicly interact Catenin is a molecule which serves as an adaptor between the receptor and the cytoskeleton -Highly regulated by phosphatases which stimulate the interaction or kinases which inhibit it (meaning phosphorylation inhibits it) slide 14 This is a term that means adhesive interaction between axons This makes a long distance journey more efficient In some cases you can have a few axons that find its way and then other axons follow them Slide 15 Answer = a You could make antibodies that recognized specific structures in the nervous system Some of the early markers recognized neural adhesion molecules -Fas I and II are examples of these molecules Fas II is expressed when it is going on a longitudinal path while Fas 1 is through the horizontal (I think it’s called kamarsual bundle) The answer is A because only one of these molecules are being expressed at a certain time -If it was heterophilic, you would see the expression of both at certain times slide 17 The neurons were going in a directed way towards the ventral midline as if they were sensing something So he hypothesized that there was something at the ventral midline that the commissural neurons were sensing -In this case, they’re referring to the floor plate because that induces the commissural neurons to grow towards the floor plate So what would you be able to do to find out what the molecule was? Slide 18 Answer = c An explant assay is a useful way to probe for the activity Take cells from rough plate and culture them in a gel -If we present them with a piece of FP tissue, they grow axon
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