Genes and Development CVHS Chapter 16

Development All the changes that occur during an organism’s lifetime Cell specialization: Cell determination: specific patterns of gene activity Cell differentiation: final step of cell specialization 16_03CellSignaling_A.swf

Morphogenesis The development of the body plan Requires two steps: Cell differentiation Maternal Influences: cytoplasmic determinants Spatial organization These depend on: Pattern formation, cell signaling, cell shapes, cell migrations Regulatory genes that turn other genes on and off at appropriate times Homeotic Genes (Hox Genes)

(a) Cytoplasmic determinants in the egg (b) Induction by nearby cells Unfertilized egg Early embryo (32 cells) Sperm Nucleus Fertilization Molecules of two different cytoplasmic determinants Zygote (fertilized egg) NUCLEUS Signal transduction pathway Mitotic cell division Figure 16.3 Sources of developmental information for the early embryo Signal receptor Two-celled embryo Signaling molecule (inducer) 18_19HeadTailAxisFruitFly_A.swf 4

Zygote The fertilized egg that develops into all the specialized cells needed within a multicellular organism Each specialized type of cell makes a unique set of proteins This is true despite the fact that these cells show nuclear equivalence – in other words they have the same genes

Master regulatory gene myoD Figure 16.4-3 Nucleus Master regulatory gene myoD Other muscle-specific genes DNA Embryonic precursor cell OFF OFF mRNA OFF MyoD protein (transcription factor) Myoblast (determined) Figure 16.4-3 Determination and differentiation of muscle cells (step 3) mRNA mRNA mRNA mRNA Myosin, other muscle proteins, and cell cycle– blocking proteins MyoD Another transcription factor Part of a muscle fiber (fully differentiated cell) 6

Cloning A new individual that is genetically identical In plants: have been able to make a clone from somatic (body) cells of an adult plant In animals: have produced clones by transferring the nucleus of a cell into an enucleated egg cell 1996: Dolly – cloned sheep in Scotland Other mammals have been cloned since Problems: only 1% - 2% success rate; high incidence of genetic defects

Dolly the Sheep

Rainbow and CC Cloned at Texas A & M in 2001, CC (copy cat) is not the same color as her clone, Rainbow & they have different temperments.

Human cloning Reproductive cloning – goal is making a new individual… very controversial and ‘banned’ Therapeutic cloning – goal is NOT making a new person but producing stem cells

Stem Cells Undifferentiated cells that can divide to produce differentiated cells and retain the ability to reproduce themselves Totipotent: potential to give rise to all body tissues Pluripotent: more specialized; can give rise to many but not all types of cells

Stem cells… Potential uses: Potential sources: Cures for degenerative diseases such as Parkinson’s Potential sources: Unused human embryos from fertility clinics and newborn’s umbilical cord blood

Parkinson’s Disease Degenerative Brain cell disorder that causes movement difficulties. Linked possibly to a specific protein within brain cells.

Control of cellular DNA expression Differential gene expression (Ch. 13) Genomic rearrangements: physical changes in the structure of the gene eg: immune system cells do this in order to produce new antibodies in response to infection Gene amplification: the copies of a particular gene are increased so that the amount of transcription of that gene can be increased

Genetic control of development: Very similar controls exist in a wide variety of organisms: The basic mechanism evolved early and has been maintained although modified Maternal effect genes: Organize the structure of the egg cell Help establish the polarity of the embryo: dorsal/ventral and anterior/posterior Homeotic genes: Specify the developmental plan for each body part

Genetic control of development… Induction: cell differentiation is influenced by interactions with neighboring cells Chronogenes: involved in developmental timing Apoptosis – programmed cell death Eg: skin between human fingers

Cancer and Cell Development All forms of cancer have one thing in common: no divisional regulation of cells Tumor: a localized group of cells with uncontrolled cell division Metastasis – cancer cells ‘escape’ and spread to other parts of the body Tumors that can metastasize are malignant

Cancer and Cell Development… Genes that control cell division: Proto-oncogenes – normal genes that control cell division Mutations can change these into oncogenes – cancer genes Some viruses carry oncogenes Tumor suppressor genes – also put the ‘brakes’ on cell division Mutations can turn off these genes and therefore stop the suppression of a tumor

P 53 & RAS Gene Mutations Mutations in the ras proto-oncogene and p53 tumor-suppressor gene are common in human cancers Mutations in the ras gene can lead to production of a hyperactive Ras protein and increased cell division

Ras protein active with or without growth factor. Figure 16.17 1 Growth factor 3 G protein Ras 6 5 Protein that stimulates the cell cycle NUCLEUS GTP Transcription factor (activator) 2 Receptor 4 Protein kinases MUTATION Ras NUCLEUS Figure 16.17 Normal and mutant cell cycle–stimulating pathway Overexpression of protein Transcription factor (activator) GTP Ras protein active with or without growth factor. 20

Protein kinases Protein that inhibits the cell cycle NUCLEUS UV light Figure 16.18 2 Protein kinases Protein that inhibits the cell cycle NUCLEUS UV light 1 DNA damage in genome 3 Active form of p53 Inhibitory protein absent Figure 16.18 Normal and mutant cell cycle–inhibiting pathway Defective or missing transcription factor UV light MUTATION DNA damage in genome 21