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Lecture 23

Biology 2581B Lecture 23: Developmental Genetics

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Biology 2581B
L.Graham Smith

Lecture 23: Developmental Genetics Determining a pathway - How does one gene affect the expression of another? o You can follow expression patterns - Example: in Drosophila, imaginal discs are an area which develops into wings - In the wingless mutant, we see red - Wingless is required for proper vestigial positioning within the development of imaginal discs - Expression of vestigial depends on the presence of wingless, and it has to be in neighbouring cells - By looking at expression patterns we can find out a lot about these two proteins, and what impact they have on each other o One is required for the other's positioning - We can also analyze a bunch of double mutants - Compare double mutant phenotype to single mutant phenotype - Different possible outcomes - Imagine we have mutant that has a knockout, with its associated phenotype - What are the possibilities if we have a double mutant? - If you do a double mutant, they could possibly be acting in two different pathways - We are most interested in number 4 - If double mutant only shows phenotype of A or B, then we know that B is potentially epistatic to gene A Epistasis in the secretion pathway - Imagine this scenario: in the cell, you have all kinds of organelles (Golgi, ER) - Vesicles migrate to outside of cell, fuse to PM, and release molecule outside the cell - What would an AB double mutant look like? - Double mutant would look like A - If the vesicles aren't getting loaded, it doesn't matter what happens after - So you will end up with a mutant that looks a lot like A - This means A is acting before B Epistasis in the pathway for vulva formation - Imagine you have a signal that activates a protein, which activates a whole chain of proteins - At some point, initiates formation of vulva (part of female reproduction system) - Imagine different mutants - You could have gain of function mutant: assume that let60 is much more expressed than the WT o Will activate a lot of the next protein, which activates a lot of the next protein o Results in increased vulva formation - Loss of function of mek-2 will result in no vulva formation - What will double mutant look like? - Double mutant will look like a mek-2 knockout because it doesn't matter that let60 is increased because eventually you'll hit the roadblock at mek-2 where nothing else happens in the pathway Epistasis - Refers to the ability of the activity of one gene to mask the activity of another gene - Secretion example: two loss of function mutations – double mutant looks like A o So A acts before B = A is epistatic to B - Vulva example: one gain of function and one loss of function mutation – double mutant looks like mek-2 - LET-60 acts before MEK-2, so MEK-2 is epistatic to LET-60 - Epistasis defines order, HOWEVER, you need to know something about the type of mutation Drosophila development - You have multinucleated embryos where you have lots of nuclei in the center of the developing embryo o Called the multinucleate syncytium - At some point, all the nuclei start migrating to the outside of the embryo - You can start to see there's some differentiation between the front and back ends of the embryo Early on… - In the embryo initially: maternally supplied components/proteins - That means mutations that are affecting early embryogenesis are mutations in the mother Maternal effect genes - Offspring looks like the genotype of the mother - If a mother is heterozygous, her offspring will look normal even if the offspring is genetically homozygous for the mutation - If the mother is homozygous for the mutation her offspring will look mutant even if the offspring is genetically heterozygous for the mutation - TWO important groups: genes required for normal anterior development, and genes required for normal posterior development - Many genes and proteins are required for embryo development; complex process - Maternal effect genes - Many proteins in the embryo are made from the mother - If one of the genes gets mutated, you can see the phenotype in the next generation - The mutation has to be in the mother - Mother might not be able to make a particular protein, but you won't see it in the mother o This mutation
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