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ch 19 genetic analysis development.docx

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University of Toronto Mississauga
Karen Williams

CH. 19: Genetic Analysis of Development -genes program development Basic Events of Development -development: process of regulated growth that results from the interaction of the genome with the cytoplasm and the extracellular external environment and that involves a programmed sequence of cellular level phenotypic events that are typically irreversible. -for a multicellular organism, development starts when a zygote is formed by fusion of sperm and egg. -The zygote is totipotent (meaning that the cell has the potential to develop into any cell type of the complete organism - Cells later in development may also be totipotent; this is common in plants, but uncommon in animals past the four cell embryo stage. -the ability of a cell to become different cell types during development is called developmental potential. -as development progresses, the developmental potential of most cells decrease -fate of the cell: what the cell will become -more specifically, the fates of all the cells in an embryo can be followed, resulting in the construction of a fate map (which is the diagram of the fate of each cell of an embryo) -when the genetic program sets the fate of a cell, the cell is said to be determined, and the process is called determination -this is still a relatively early stage of development, so although a determined cell is molecularly different, it is not morphologically distinct from its neighbors. -the cellular changes that occur during determination are directed and lead to a stable state. I.e once the fate of the cell is determined, it does not change. Thus a determined cell has 0 developmental potential (there is no longer a range of cell types that the cell can become) -the are two principal mechanisms for cell determination -in most cases cell determination occurs by induction; that is, an inductive signal by one cell or group of cells affects the development of another cell or group of cells -for example, the signal can move by diffusion through the space between cell and be detected by a surface receptor on the target cell -or, cells in contact can lead to interaction of transmembrane proteins in the plasma membranes, resulting in the production of the signal in one cell type. -differentiation: the process by which determined cells undergo cell specific developmental programs to produce cell types with specific identities, such as nerve cells, anti-body producing cells, skins cells and so on in animals; leaf guard cells, meristematic cells, and so on in plants -differentiuation in most cases results from differential gene expression, rather than from a differential loss of DNA that leaves different sets of genes in different cell types. That is, expression of different sets of genes in different kinds of determined cells leads to different proteins in the cells, and the proteins guide the progression to the various differentiated states -morphogenesis: the developmental process by which anatomical structures or cell shape and size are generated and organized, produced by a regulated pattern of cell division Model Organisms for genetic analysis of development -Saccharomyces cerevisiae: single-celled organism yeast has a limited developmental repertoire, but notably yeast cells signal each other though secreted extracellular pheromones as an essential part of mating. The actual differentiation of yeast cells into the two mating types has similiarities to developmental processes found in multicellular organisms -Drosophila melanogaster: fruit fly. The study of Drosophila developmental mutatnts is providing a rich array of data about the molecular aspects of development. -Caenorhabditis elegans: nematode worm -arabidopsis thaliana: small plant -Danio rerio: zebra fish -mus musculus: mouse. Particularly close to humans Developmental results from differential gene expression Constancy of DNA in the Genome during development -cloning: generating individuals genetically identical to the starting individual -DNA remains constant during development Regenertation of Carrot plants from mature single cells -Steward -found that the DNA content of a cell remains constant during development Cloning Animals -Wilmut’s (sheep cloning) group tested the ability of nuclei from embryonic, fetal, and adult cells to direct the development of sheep. Their experimental approach was as follows: 1. embryonic cells, fetal fibroblast cells, and mammary epithelial cells were grown in tissue culture and then induced to enter a quiescent state by reducing the concentration of the growth serum 2. the cells were fused with enucleated oocytes with enucleated oocytes (egg cells), and the fusion cells were allowed to grow and divide for 6 days to produce embryos 3. the embryos were implanted into recipient ewes, and the establishment and progression of pregnancy was monitored -the results were as follows: all produced a child (very limited though as in 1 of 277 for mammary epithelium). The baby ewe was a clone of the donor ewe and not the implanted ewe -demonstrates that the adult nucleuis contains all the genetic information required to specify a new organism -Summary: although the success rate for the experiment was not high (for technical reasons), the highly significant accomplishment here was the development of a live lamb directed by an adult nucleus. Cloning technology is applicable to humans, and the ethical issues it raises continues to be debated Mammal cloning problems -process is inefficient - calico cat cloning summary -whil Cc (the cloned cat) and Rainbow (mother of CC) are genitically identical. This fact argues that the genetic program is not alone in specifying the adult organism. Notably, environmental factors play an important role -more serious problems than variations in coat and color and personality have turned up in cloned animals -mammal cloning is extremely inefficient; usually, most clones die before or soon after birth. The few survivors seem to exhibit varying degrees of developmental abnormalities, suggesting problems at the gene expression level Examples of differential gene activity during development Hemoglobin types and human development -globin gene expression switches during human development, and this switching involves a sophisticated gene regulatory system that turns appropriate globin genes on and off over a long time period Polytene chromosome puffs during dipteran (two-winged fly) development -polytene chromosomes: a special type of chromosome that consists of a bundle of chromatids produced by repeated cycles of chromosome duplication without nuclear division, and that they are readily visible after staining under the light microscope -at characterisitic times during dev. Specific bands unwind locally to form puffs. -the puffing occurs as a result of very high levels of gene transcription. Puffing is hunder hormonal control. … SUMMARY: development results from differential gene activity of a genome that contains a constant amount of DNA from the zygote stage to the mature organism stage. Nonetheless, the genes are only part of the question for development ; environmental factors can affect the phenotypic differences in cloned mammals from the parent that donated the nucleus for cloning Exception to the constancy of genomic DNA during development: DNA loss in antibody-producing cells -there are a few exceptions to the rule that no DNA is lost during development. One such example involves the loss of genetic information during the development of cells that produce antibodies Antibody molecules -the cells responsible for immune specificity are lymphocytes, specifically T cells and B cells -B lymphocytes develop in adult bone marrow. -When activated by an antigen, B cells develop into plasma cells that make proteins called antibodies -antibody molecules are inserted in the plasma membrane of the plasma cells, and they are also released into the blood and lymph, where they are responsible for the humoral immune responses. -the antibodies bind specifically to the antigens that stimulate their production -the establishment of immunity against a particular antigen results from clonal selection. This is a process whereby cells that have antibodies displayed on their surfaces that are specific for the antigen are stimulated to proliferate and secrete that antibody. During development, each lymphocyte becomes committed to react with a particular antigen, even though the cell has never been exposed to the antigen -all antibody molecules made by a given plasma cell are identical (they have the ame protein chains and the bind the same antigen). -As a group, antibodies are proteins called immunoglobulins (Igs). -5 major classes of antibodies are found in mammals: IgA, IgD, IgE, IgG, and IgM. Each class has a different type of H chain: alpha, delta, epsilon, gamma, and mu. Two types of L chains are found: kappa and
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