Development, Stem Cells, and Cancer 16 Development, Stem Cells, and Cancer

Concept 16.1: A program of differential gene expression leads to the different cell types in a multicellular organism transformation from zygote to adult results from cell division, cell differentiation, and morphogenesis Cell differentiation - process by which cells become specialized in structure and function Morphogenesis - the processes that give an organism its shape 2

(a) Fertilized eggs of a frog (b) Newly hatched tadpole Figure 16.2 Figure 16.2 From fertilized egg to animal: What a difference four days makes. 1 mm 2 mm (a) Fertilized eggs of a frog (b) Newly hatched tadpole 3

(a) Cytoplasmic determinants in the egg (b) Induction by nearby cells Figure 16.3 (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) 4

Induction - signal molecules from embryonic cells cause transcriptional changes in nearby target cells 5

Sequential Regulation of Gene Expression During Cellular Differentiation Determination commits a cell irreversibly to its final fate Determination precedes differentiation 6

Master regulatory gene myoD Figure 16.4-1 Nucleus Master regulatory gene myoD Other muscle-specific genes DNA Embryonic precursor cell OFF OFF Figure 16.4-1 Determination and differentiation of muscle cells (step 1) 7

Master regulatory gene myoD Figure 16.4-2 Nucleus Master regulatory gene myoD Other muscle-specific genes DNA Embryonic precursor cell OFF OFF mRNA OFF MyoD protein (transcription factor) Myoblast (determined) Figure 16.4-2 Determination and differentiation of muscle cells (step 2) 8

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) 9

Apoptosis: A Type of Programmed Cell Death Apoptosis is the best-understood type of “programmed cell death” 10

Cells undergoing apoptosis Figure 16.6 1 mm Interdigital tissue Cells undergoing apoptosis Space between digits Figure 16.6 Effect of apoptosis during paw development in the mouse 11

Genetic Analysis of Early Development: Scientific Inquiry Edward B. Lewis, discovered the homeotic genes, which control pattern formation in late embryo, larva, and adult stages 12

Wild type Mutant Eye Leg Antenna Figure 16.8 Figure 16.8 Abnormal pattern formation in Drosophila Leg Antenna 13

Totipotent cells Cells that can give rise to all specialized cell types are called totipotent 14

Egg with donor nucleus activated to begin development Figure 16.11 Experiment Frog embryo Frog egg cell Frog tadpole UV Fully differ- entiated (intestinal) cell Less differ- entiated cell Donor nucleus trans- planted Donor nucleus trans- planted Enucleated egg cell Egg with donor nucleus activated to begin development Results Figure 16.11 Inquiry: Can the nucleus from a differentiated animal cell direct development of an organism? Most develop into tadpoles. Most stop developing before tadpole stage. 15

genetically identical to mammary cell donor Results Figure 16.12 Technique Mammary cell donor Egg cell donor 1 2 Nucleus removed Cultured mammary cells Egg cell from ovary 3 Cells fused Cell cycle arrested, causing cells to dedifferentiate Nucleus from mammary cell 4 Grown in culture Early embryo Figure 16.12 Research method: reproductive cloning of a mammal by nuclear transplantation 5 Implanted in uterus of a third sheep Surrogate mother 6 Embryonic development Lamb (“Dolly”) genetically identical to mammary cell donor Results 16

Figure 16.13 Figure 16.13 CC, the first cloned cat (right), and her single parent 17

Stem Cells of Animals A stem cell - unspecialized cell that can differentiate into specialized cells of one or more types 18

Cell division White blood cells Figure 16.14 Stem cell Cell division Stem cell and Precursor cell Figure 16.14 How stem cells maintain their own population and generate differentiated cells Fat cells or Bone cells or White blood cells 19

Embryonic stem cells Adult stem cells Figure 16.15 Embryonic stem cells Adult stem cells Cells that can generate all embryonic cell types Cells that generate a limited number of cell types Cultured stem cells Different culture conditions Figure 16.15 Working with stem cells Different types of differentiated cells Liver cells Nerve cells Blood cells 20

Embryonic Stem (ES) cells are pluripotent, capable of differentiating into many cell types Researchers using retroviruses can reprogram fully differentiated cells to act like ES cells Cells transformed this way are called iPS, or induced pluripotent stem cells 21

Concept 16.3: Abnormal regulation of genes that affect the cell cycle can lead to cancer The gene regulation systems that go wrong during cancer are the same systems involved in embryonic development 22

Types of Genes Associated with Cancer oncogenes - cancer-causing genes The normal version of these genes, called proto-oncogenes, code for proteins that stimulate normal cell growth and division 23

within the gene within a control element Figure 16.16 Proto-oncogene Proto-oncogene Proto-oncogene Translocation or transposition: gene moved to new locus, under new controls Gene amplification: multiple copies of the gene Point mutation: within the gene within a control element Oncogene Oncogene Oncogene New promoter Figure 16.16 Genetic changes that can turn proto-oncogenes into oncogenes Normal growth- stimulating protein in excess Normal growth- stimulating protein in excess Normal growth- stimulating protein in excess Hyperactive or degradation- resistant protein 24

Tumor-suppressor genes encode proteins that help prevent uncontrolled cell growth 25

Inherited Predisposition and Other Factors Contributing to Cancer Individuals can inherit oncogenes or mutant alleles of tumor-suppressor genes 26

DNA breakage can contribute to cancer, thus the risk of cancer can be lowered by minimizing exposure to agents that damage DNA, such as ultraviolet radiation and chemicals found in cigarette smoke Also, viruses play a role in about 15% of human cancers by donating an oncogene to a cell, disrupting a tumor-suppressor gene, or converting a proto-oncogene into an oncogene 27