CAMPBELL BIOLOGY IN FOCUS Urry Cain Wasserman Minorsky

CAMPBELL BIOLOGY IN FOCUS Urry • Cain • Wasserman • Minorsky • Jackson • Reece 16 Development, Stem Cells, and Cancer Lecture Presentations by Kathleen Fitzpatrick and Nicole Tunbridge © 2014 Pearson Education, Inc.

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 © 2014 Pearson Education, Inc.

Figure 16. 2 1 mm (a) Fertilized eggs of a frog © 2014 Pearson

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 © 2014 Pearson Education, Inc.

• Assist with gene expression regulation during cell differentiation (after fertilization) • Cytoplasmic determinants are distributed unequally in cytoplasm • The same determinants tend to stay together © 2014 Pearson Education, Inc.

2 nd 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 © 2014 Pearson Education, Inc.

Figure 16. 3 (a) Cytoplasmic determinants in the egg (b) Induction by nearby cells Unfertilized egg Sperm Early embryo (32 cells) Nucleus Fertilization Zygote (fertilized egg) Mitotic cell division Two-celled embryo © 2014 Pearson Education, Inc. Molecules of two different cytoplasmic determinants NUCLEUS Signal transduction pathway Signal receptor Signaling molecule (inducer)

Sequential Regulation of Gene Expression During Cellular Differentiation § Determination process that commits a

§ Determination precedes differentiation § In a fully differentiated cell, transcription is the primary regulatory point for maintaining gene expression § Becomes specialized at making tissue-specific proteins © 2014 Pearson Education, Inc.

§ Ex. Determination and Differentiation of a Muscle Cell § Signals from other cells lead to an activation of a master regulatory gene (myo. D) § Makes a transcription factor that acts as an activator § Now committed to a muscle cell § Above process: determination © 2014 Pearson Education, Inc.

Apoptosis: A Type of Programmed Cell Death § Apoptosis: “programmed cell death” § Occurs

Figure 16. 6 1 mm Interdigital tissue Cells undergoing apoptosis Space between digits ©

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 © 2014 Pearson Education, Inc.

Pattern formation: setting up the body plan (head, tail, L/R, back, front) as a result of cytoplasmic determinants and inductive signals

Homeotic Genes: master control genes that control pattern formation (eg. Hox genes) Mutations in homeotic genes cause misplacement of structures.

Evolving Switches, Evolving Bodies HHMI SHORT FILM

Pitx 1 Gene = Homeotic/Hox Gene STICKLEBACK FISH HUMANS Development of pelvic bone Development of anterior structures, brain, structure of hindlimb Mutation may cause clubfoot, polydactyly (extra fingers/toes), upper limb deformities

CHAPTER 16. 2 Cloning of organisms showed that differentiated cells could be “reprogrammed” and ultimately lead to the production of stem cells

Cloning Plants and Animals © 2014 Pearson Education, Inc.

Totipotent cells § Cells that can give rise to all specialized cell types are

§ Researcher John Gurdon found that when early frog embryo nuclei were transplanted into enucleated eggs, most developed into tadpoles § With nuclei from fully differentiated cells, most did not develop © 2014 Pearson Education, Inc.

Figure 16. 11 Experiment Frog egg cell Frog embryo Frog tadpole UV Results © 2014 Pearson Education, Inc. Less differentiated cell Fully differentiated (intestinal) cell Donor nucleus transplanted Enucleated egg cell Egg with donor nucleus activated to begin development Most develop into tadpoles. Most stop developing before tadpole stage.

• Similar outcome occurred with cloning mammals • Clones tend to have some

Figure 16. 13 © 2014 Pearson Education, Inc.

Figure 16. 12 Technique Mammary cell donor 1 Cultured mammary cells Egg cell donor 2 3 Cells fused Cell cycle arrested, causing cells to dedifferentiate 4 Grown in culture Nucleus removed Egg cell from ovary Nucleus from mammary cell Early embryo 5 Implanted in uterus of a third sheep Surrogate mother 6 Embryonic development Results © 2014 Pearson Education, Inc. Lamb (“Dolly”) genetically identical to mammary cell donor

• https: //www. youtube. com/watch? v=q 0 B 9 Bn 1 WW_4 ©

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 © 2014 Pearson Education, Inc.

Figure 16. 14 Stem cell Cell division Stem cell and Fat cells © 2014

§ Two types of stem cells: § Embryonic: can differentiate into any type of

Figure 16. 15 Embryonic stem cells Cells that can generate all embryonic cell types Adult stem cells Cells that generate a limited number of cell types Cultured stem cells Different culture conditions Liver cells Nerve cells Blood cells Different types of differentiated cells © 2014 Pearson Education, Inc.

§ However…. § Researchers using retroviruses can now reprogram fully differentiated cells to act like ES cells § Cells transformed this way are called i. PS, or induced pluripotent stem cells © 2014 Pearson Education, Inc.

Concept 16. 3: Abnormal regulation of genes that affect the cell cycle can lead to cancer § Two factors that can affect the cell cycle and lead to cancer: § Changes to proto-oncogenes § Abnormal tumor suppressor genes © 2014 Pearson Education, Inc.

§ Proto-oncogenes: genes that code for proteins that stimulate normal cell growth and division § Through genetic changes, proto-oncogenes can become oncogenes § Oncogenes - cancer-causing genes © 2014 Pearson Education, Inc.

Figure 16. 16 Proto-oncogene Translocation or transposition: gene moved to new locus, under new controls Proto-oncogene Gene amplification: multiple copies of the gene Point mutation: New Oncogene promoter Normal growthstimulating protein in excess © 2014 Pearson Education, Inc. Normal growthstimulating protein in excess within a control element within the gene Oncogene Normal growthstimulating protein in excess Hyperactive or degradationresistant protein

§ Tumor-suppressor genes encode proteins that help prevent uncontrolled cell growth § Mutations can

Inherited Predisposition and Other Factors Contributing to Cancer § Individuals can inherit oncogenes or

§ 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 § https: //www. youtube. com/watch? v=9 J 8 c. MW 94 VUs © 2014 Pearson Education, Inc.