Development, Stem Cells & Cancer PDF

Here's the transcription of the provided document and images into a structured markdown format: # Ch. 15 Warm-Up 1. Compare DNA methylation and histone acetylation. 2. What is the role of activators vs. repressors? Where do they bind to? 3. List the components found in a eukaryotic transcriptio...

Here's the transcription of the provided document and images into a structured markdown format: # Ch. 15 Warm-Up 1. Compare DNA methylation and histone acetylation. 2. What is the role of activators vs. repressors? Where do they bind to? 3. List the components found in a eukaryotic transcription initiation complex. 4. What is the function of miRNAs and siRNAs? # Ch. 16 Warm-Up 1. List and describe the 3 processes that are involved in transforming a zygote. 2. Compare oncogenes, proto-oncogenes, and tumor suppressor genes. 3. What are the roles of the ras gene and the p53 gene? # Development, Stem Cells & Cancer Chapter 16 What you must know: How timing and coordination of specific events are regulated in normal development, including pattern formation and induction. The role of gene regulation in embryonic development and cancer. # Chapter 16.1 A program of differential gene expression leads to the different cell types in a multicellular organism # Embryonic Development: Zygote → Organism The image shows a fertilized frog's eggs alongside a newly hatched tadpole. 1. Cell Division: large number of identical cells through mitosis 2. Cell Differentiation: Cells become specialized in structure & function 3. Morphogenesis: "creation of form" – organism's shape **Cytoplasmic determinants:** maternal substances in egg distributed unevenly in early cells of the embryo. *(a) Cytoplasmic determinants in the egg is an illustration showing:* * Molecules of two different cytoplasmic determinants * Nucleus * Unfertilized egg * Fertilization * Mitotic cell division * Sperm * Zygote (fertilized egg) * Two-celled embryo **Induction:** cells triggered to differentiate **Cell-Cell Signals:** molecules produced by one cell influences neighboring cells Eg. Growth factors *(b) Induction by nearby cells is an illustration showing:* * Signaling molecule * Signal receptor * Signal transduction pathway * Early embryo (32 cells) * Nucleus Determination: irreversible series of events that lead to cell differentiation Image provides the following illustrative content: * Oocyte * Sperm * Totipotent - Morula * Pluripotent - Inner Mass Cells * Blastocyst * Human Fetus * Circulatory System * Nervous System * Immune System * Unipotent Regulatory genes and transcription factors direct cell differentiation The image provides illustration of: * Nucleus * Master regulatory gene *myoD* * Other muscle-specific genes * DNA * Embryonic precursor cell * Myoblast (determined) * Part of muscle fiber (fully differentiated cell) * mRNA * MyoD protein (transcription factor) * MyoD * A different transcription factor- * Myosin, other muscle proteins, and cell cycle-blocking proteins # Role of Apoptosis * Most of the embryonic cells are produced in excess * Cells will undergo apoptosis (programmed cell death) to sculpture organs and tissues * Carried out by caspase proteins * Image shows a limb with interdigital tissue undergoing apoptosis leading to the formation of digits. * Image shows cells undergoing apoptosis with space between digits. The image shows Apoptosis of a human white blood cell. # Pattern formation: setting up the body plan The images illustrate the process in the development of an embryo. In figure (a), we see an adult insect. (b) shows Development from egg to larva. The text describes the body axes. including: * Dorsal * Anterior * Posterior * Left, Right * Ventral The image describes 5 stages: 1. Developing egg 2. Mature, unfertilized egg 3. Fertilized egg 4. Segmented embryo 5. Larva **Morphogens**: uneven distribution of substances that establish an embryo’s axes The image shows a visual representation of how morphogens, specifically Bicoid mRNA and protein, are distributed in an unfertilized egg and early embryo and illustrates where morphogens are distributed in the formation on the head or anterior. **Homeotic Genes**: master control genes that control pattern formation (eg. Hox genes) The image shows two insects side by side. One is a Wild type the other is Mutant that shows mutations in homeotic genes that cause misplacement of structures. *For Example:* The wild type has antenna and an eye. *For Example:* The mutant has instead of an antenna, it has legs in place of the antenna. # Evolving Switches, Evolving Bodies Pitxi1 Gene = Homeotic/Hox Gene Stickleback Fish Development of pelvic bone **Humans** Development of anterior structures, brain, structure of hindlimb Mutation may cause clubfoot, polydactyly (extra fingers/toes), upper limb defect # Chapter 16.2 Cloning of organisms showed that differentiated cells could be "reprogrammed" and ultimately lead to the production of stem cells **Cloning Organisms - Nuclear transplantation:** nucleus of egg is removed and replaced with The image illustrates cloning through nuclear transplantation and describes these steps: 1. Mammary cell donor - Cultured mammary cells 2. Egg cell donor - Egg cell from ovary 3. Cells fused - Nucleus removed 4. Grown in culture - Nucleus from mammary cell 5. Implanted in uterus of a third sheep - Early embryo - Surrogate mother 6. Embryonic development Result: Lamb ("Dolly") genetically identical to mammary cell donor **Problems with Reproductive Cloning** * Cloned embryos exhibited various defects * DNA of fully differentiated cells have epigenetic changes **Stem Cells** * Stem cells: can reproduce itself indefinitely and produce other specialized cells * Zygote = totipotent (any type of cell) * Embryonic stem (ES) cells = pluripotent (many cell types) * Adult stem cells = multipotent (a few cell types) or induced pluripotent, iPS ("deprogrammed" to be pluripotent) **Embryonic vs. Adult stem cells** Illustrative content: * Embryonic stem cells - Cells that can generate all embryonic cell types (cultured stem cells) * Adult stem cells - Cells that generate a limited number of cell types (different culture conditions) * Different types of differentiated cells * Liver cells, Nerve cells, Blood cells Using stem cells for disease treatment Illustrative content: 1. Remove skin cells from patient. 2. Reprogram skin cells so the cells become induced pluripotent stem (iPS) cells. 3. Treat IPS cells so that they differentiate into a specific cell type. 4. Return cells to patient, where they can repair damaged tissue. # Chapter 16.3 Abnormal regulation of genes that affect the cell cycle can lead to cancer Control of Cell Cycle: 1. Proto-oncogene = stimulates normal cell growth 2. Tumor-suppressor gene = inhibits cell division Illustrating Effects of Mutations. * Protein overexpressed (such as Ras). Cell cycle overstimulated leads to increased cell division. * Protein absent (such as p52). Cell cycle not inhibited. Proto-Oncogene to Oncogene * Gene that stimulates normal cell growth & division * Mutation in proto-oncogene * Cancer-causing gene Effects: * Increase product of proto-oncogene * Increase activity of each protein molecule produced by gene Proto-oncogene to Oncogene * Proto-oncogene to Proto-oncogene: Translocation or transposition, Gene amplification, * New Oncogene promoter * Normal growth-stimulating protein in excess * Proto-oncogene: Point mutation within a control element * Normal growth - stimulating protein in excess * Oncogene * Proto-oncogene: Point mutation within the gene * Hyperactive or degradation-resistant protein **Genes involved in cancer:** * **Ras gene**: proto-oncogene * Stimulates cell cycle * Mutations of ras occurs in 30% of cancers * **p53 gene**: tumor-suppressor gene * Functions: halt cell cycle for DNA repair, turn on DNA repair, activate apoptosis (cell death) * Mutations of p53 in 50+% of cancers Ras gene * Image details and compares normal and Mutant cell cycle stimulating pathways, describing the proteins involved in each. The primary protein in the image is "Ras" p53 gene * Image details an compares normal and Mutant cell cycle inhibiting pathways, describing the proteins involved in each. The primary protein described in the image is "p53" Illustrative content: There are normal and abnormal views if a colon. 1. Normal colon epithelial cells 2. Colon 3. Colon Wall 4. Small benign growth (polyp) 5. Activation of as oncogene 6. Loss of tumor-suppressor gene SMAD4 7. Large benign growth (adenoma) 8. Loss of tumor-suppressor gene p53 - Additional mutations 9. Malignant tumor (carcinoma) Cancer results when mutations accumulate (5-7 changes in DNA) * Active oncogenes + loss of tumor-suppressor genes * The longer we live, the more likely that cancer might develop How does chemotherapy work? Chemotherapy drugs block hormone attachment ("binding") to their receptors and block growth as illustrated with the following components: * Hormone-receptor binding blocked * Cell * STOP GROWING! * Receptor positive cells may stop growing with Chemotherapy treatment Chemotherapy blocks hormones from binding to their receptors. This sends a message to the cells to "Stop growing!" Cells that are receptor positive receive the "stop growing" message better than cells that do not have the receptors (triple negative breast cancer cells). What is Triple Negative Breast Cancer (TNBC)? Visual illustration comparing: * Receptor Positive Breast Cancer * Triple Negative Breast Cancer Many breast cancer cells have 1, 2 or even all 3 of these important receptors on their surface. These receptors are important targets for Chemotherapy to block hormone attachment and block the growth of the abnormal cells. Doctors take a piece of the tissue to test how many of these receptors are present. In Triple Negative Breast Cancer (TNBC), none of the 3 important receptors are found on the cell surface. This makes it difficult to use traditional chemotherapy to block growth. Summary * Embryonic development occurs when gene regulation proceeds correctly * Cancer occurs when gene regulation goes awry