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

Cytoplasic Determinants and Inductive Signals Two factors that control cell differentiation include: Cytoplasmic determinants: maternal substances (RNA and proteins-including transcription factors) encoded by the mother’s DNA) found in the cytoplasm of an unfertilized egg

Assist with gene expression regulation during cell differentiation (after fertilization) Cytoplasmic determinants are distributed unequally in cytoplasm The same determinants tend to stay together

2nd Factor Influencing Cell Differentiation: Induction - signal molecules from embryonic cells cause transcriptional changes in nearby target cells Helps induce differentiation of many specialized cell types Usually occurs later in embryonic development

(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) 9

Sequential Regulation of Gene Expression During Cellular Differentiation Determination process that commits a cell irreversibly to its final fate Determination precedes differentiation If a cell has undergone determination, it will still differentiate into its expected cell type 10

In a fully differentiated cell, transcription is the primary regulatory point for maintaining gene expression Become specialized at making tissue-specific proteins

Ex. Determination and Differentiation of a Muscle Cell Signals from other cells lead to an activation of a master regulatory gene (myoD) Makes a transcription factor that acts as an activator Now committed to a muscle cell Above process: determination

MyoD stimulates the regulatory gene further and activates other genes to produce other necessary transcription factors

Apoptosis: A Type of Programmed Cell Death Apoptosis is the best-understood type of “programmed cell death” Occurs in some cells during differentiation 15

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 16

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 17

Wild type Mutant Eye Leg Antenna Figure 16.8 Figure 16.8 Abnormal pattern formation in Drosophila Leg Antenna 18

Cloning Plants and Animals

Totipotent cells Cells that can give rise to all specialized cell types are called totipotent 20

Researcher John Gurdon found that when early frog embryo nuclei were transplanted into enucleated egg, most developed into tadpoles Nuclei from fully differentiated cells, most did not develop

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. 22

Process worked with mammals Clones tend to have some faulty genes affecting lifespan

Figure 16.13 Figure 16.13 CC, the first cloned cat (right), and her single parent 24

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 25

Stem Cells of Animals Main reason researchers want to clone human embryos is for the production of stem cells A stem cell - unspecialized cell that can differentiate into specialized cells of one or more types 26

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 27

Two types of stem cells: Embryonic: can differentiate into any type of cells Adult: not able to differentiate into all cell types

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 29

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 30

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 31

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 32

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 33

Tumor-suppressor genes encode proteins that help prevent uncontrolled cell growth 34

Inherited Predisposition and Other Factors Contributing to Cancer Individuals can inherit oncogenes or mutant alleles of tumor-suppressor genes 35

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 36