1. © 2011 Pearson Education, Inc.
Concept 18.4: A program of differential gene expression leads to the different cell types in a multicellular organism
During embryonic development, a fertilized egg gives rise to many different cell types
Cell types are organized successively into tissues, organs, organ systems, and the whole organism
Gene expression orchestrates the developmental programs of animals
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2. A Genetic Program for Embryonic Development
The transformation from zygote to adult results from cell division, cell differentiation, and morphogenesis
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3. (a) Fertilized eggs of a frog (b) Newly hatched tadpole
Figure 18.16
Figure 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

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Cell differentiation is the process by which cells become specialized in structure and function
The physical processes that give an organism its shape constitute morphogenesis
Differential gene expression results from genes being regulated differently in each cell type
Materials in the egg can set up gene regulation that is carried out as cells divide
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5. Cytoplasmic Determinants and Inductive Signals
An egg’s cytoplasm contains RNA, proteins, and other substances that are distributed unevenly in the unfertilized egg
Cytoplasmic determinants are maternal substances in the egg that influence early development
As the zygote divides by mitosis, cells contain different cytoplasmic determinants, which lead to different gene expression
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6. (a) Cytoplasmic determinants in the egg (b) Induction by nearby cells
Figure 18.17
(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
NUCLEUS
Zygote (fertilized egg)
Signal transduction pathway
Mitotic cell division
Figure Sources of developmental information for the early embryo.
Signal receptor
Two-celled embryo
Signaling molecule (inducer)

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The other important source of developmental information is the environment around the cell, especially signals from nearby embryonic cells
In the process called induction, signal molecules from embryonic cells cause transcriptional changes in nearby target cells
Thus, interactions between cells induce differentiation of specialized cell types
Animation: Cell Signaling
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8. (b) Induction by nearby cells
Figure 18.17b
(b) Induction by nearby cells
Early embryo (32 cells)
NUCLEUS
Signal transduction pathway
Figure Sources of developmental information for the early embryo.
Signal receptor
Signaling molecule (inducer)

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Sequential Regulation of Gene Expression During Cellular Differentiation
Determination commits a cell to its final fate
Determination precedes differentiation
Cell differentiation is marked by the production of tissue-specific proteins
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Myoblasts produce muscle-specific proteins and form skeletal muscle cells
MyoD is one of several “master regulatory genes” that produce proteins that commit the cell to becoming skeletal muscle
The MyoD protein is a transcription factor that binds to enhancers of various target genes
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11. Master regulatory gene myoD
Figure
Nucleus
Master regulatory gene myoD
Other muscle-specific genes
DNA
Embryonic precursor cell
OFF
OFF
mRNA
OFF
MyoD protein (transcription factor)
Myoblast (determined)
Figure Determination and differentiation of muscle cells.
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)

12. Pattern Formation: Setting Up the Body Plan
Pattern formation is the development of a spatial organization of tissues and organs
In animals, pattern formation begins with the establishment of the major axes
Positional information, the molecular cues that control pattern formation, tells a cell its location relative to the body axes and to neighboring cells
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Pattern formation has been extensively studied in the fruit fly Drosophila melanogaster
Combining anatomical, genetic, and biochemical approaches, researchers have discovered developmental principles common to many other species, including humans
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14. The Life Cycle of Drosophila
In Drosophila, cytoplasmic determinants in the unfertilized egg determine the axes before fertilization
After fertilization, the embryo develops into a segmented larva with three larval stages
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15. Head Thorax Abdomen 0.5 mm Dorsal Right BODY AXES Anterior Posterior
Figure 18.19a
Head
Thorax
Abdomen
0.5 mm
Dorsal
Right
BODY AXES
Anterior
Posterior
Figure Key developmental events in the life cycle of Drosophila.
Left
Ventral
(a) Adult

16. 1 2 3 4 5 Follicle cell Egg developing within ovarian follicle Nucleus
Figure 18.19b
Follicle cell 1
Egg developing within ovarian follicle
Nucleus
Egg
Nurse cell 2
Unfertilized egg
Egg shell
Depleted nurse cells
Fertilization
Laying of egg 3
Fertilized egg
Embryonic development
Figure Key developmental events in the life cycle of Drosophila. 4
Segmented embryo
0.1 mm
Body segments
Hatching 5
Larval stage
(b) Development from egg to larva

17. Genetic Analysis of Early Development: Scientific Inquiry
Edward B. Lewis, Christiane Nüsslein-Volhard, and Eric Wieschaus won a Nobel Prize in 1995 for decoding pattern formation in Drosophila
Lewis discovered the homeotic genes, which control pattern formation in late embryo, larva, and adult stages
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18. Eye Leg Antenna Wild type Mutant Figure 18.20
Figure Abnormal pattern formation in Drosophila.
Wild type
Mutant

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Nüsslein-Volhard and Wieschaus studied segment formation
They created mutants, conducted breeding experiments, and looked for corresponding genes
Many of the identified mutations were embryonic lethals, causing death during embryogenesis
They found 120 genes essential for normal segmentation
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Axis Establishment
Maternal effect genes encode for cytoplasmic determinants that initially establish the axes of the body of Drosophila
These maternal effect genes are also called egg-polarity genes because they control orientation of the egg and consequently the fly
Animation: Development of Head-Tail Axis in Fruit Flies
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21. © 2011 Pearson Education, Inc.
Bicoid: A Morphogen Determining Head
Structures
One maternal effect gene, the bicoid gene, affects the front half of the body
An embryo whose mother has no functional bicoid gene lacks the front half of its body and has duplicate posterior structures at both ends
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22. Head Tail Wild-type larva 250 m Tail Tail Mutant larva (bicoid) A8 T1
Figure 18.21
Head
Tail A8 T1 T2 T3 A7 A6 A1 A5 A2 A4 A3
Wild-type larva
250 m
Tail
Tail
Figure Effect of the bicoid gene on Drosophila development. A8 A8 A7 A6 A7
Mutant larva (bicoid)

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This phenotype suggests that the product of the mother’s bicoid gene is concentrated at the future anterior end
This hypothesis is an example of the morphogen gradient hypothesis, in which gradients of substances called morphogens establish an embryo’s axes and other features
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24. Fertilization, translation of bicoid mRNA
Figure 18.22
RESULTS
100 m
Anterior end
Fertilization, translation of bicoid mRNA
Bicoid mRNA in mature unfertilized egg
Bicoid protein in early embryo
Figure Inquiry: Is Bicoid a morphogen that determines the anterior end of a fruit fly?
Bicoid mRNA in mature unfertilized egg
Bicoid protein in early embryo

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The bicoid research is important for three reasons
– It identified a specific protein required for some early steps in pattern formation
– It increased understanding of the mother’s role in embryo development
– It demonstrated a key developmental principle that a gradient of molecules can determine polarity and position in the embryo
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Concept 18.5: Cancer results from genetic changes that affect cell cycle control
The gene regulation systems that go wrong during cancer are the very same systems involved in embryonic development
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27. Types of Genes Associated with Cancer
Cancer can be caused by mutations to genes that regulate cell growth and division
Tumor viruses can cause cancer in animals including humans
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Oncogenes are cancer-causing genes
Proto-oncogenes are the corresponding normal cellular genes that are responsible for normal cell growth and division
Conversion of a proto-oncogene to an oncogene can lead to abnormal stimulation of the cell cycle
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29. within a control element
Figure 18.23
Proto-oncogene
DNA
Translocation or transposition: gene moved to new locus, under new controls
Gene amplification: multiple copies of the gene
Point mutation:
within a control element
within the gene
New promoter
Oncogene
Oncogene
Figure 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

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Proto-oncogenes can be converted to oncogenes by
Movement of DNA within the genome: if it ends up near an active promoter, transcription may increase
Amplification of a proto-oncogene: increases the number of copies of the gene
Point mutations in the proto-oncogene or its control elements: cause an increase in gene expression
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31. Tumor-Suppressor Genes
Tumor-suppressor genes help prevent uncontrolled cell growth
Mutations that decrease protein products of tumor-suppressor genes may contribute to cancer onset
Tumor-suppressor proteins
Repair damaged DNA
Control cell adhesion
Inhibit the cell cycle in the cell-signaling pathway
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32. Interference with Normal Cell-Signaling Pathways
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
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33. Protein kinases (phosphorylation cascade) Receptor
Figure 18.24a 1
Growth factor
MUTATION
Ras
Hyperactive Ras protein (product of oncogene) issues signals on its own. 3
G protein
GTP
Ras P P P P
GTP P P 4 2
Protein kinases (phosphorylation
cascade)
Receptor
NUCLEUS 5
Transcription factor (activator)
DNA
Figure Signaling pathways that regulate cell division.
Gene expression
Protein that
stimulates the cell cycle
(a) Cell cycle–stimulating pathway

34. Protein that inhibits the cell cycle
Figure 18.24b 2
Protein kinases
MUTATION
Defective or missing transcription factor, such as p53, cannot activate transcription. 3
UV light
Active form of p53 1
DNA damage in genome
DNA
Figure Signaling pathways that regulate cell division.
Protein that inhibits the cell cycle
(b) Cell cycle–inhibiting pathway

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Suppression of the cell cycle can be important in the case of damage to a cell’s DNA; p53 prevents a cell from passing on mutations due to DNA damage
Mutations in the p53 gene prevent suppression of the cell cycle
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36. Protein overexpressed Protein absent
Figure 18.24c
EFFECTS OF MUTATIONS
Protein overexpressed
Protein absent
Cell cycle overstimulated
Increased cell division
Cell cycle not inhibited
Figure Signaling pathways that regulate cell division.
(c) Effects of mutations

37. The Multistep Model of Cancer Development
Multiple mutations are generally needed for full-fledged cancer; thus the incidence increases with age
At the DNA level, a cancerous cell is usually characterized by at least one active oncogene and the mutation of several tumor-suppressor genes
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38. Loss of tumor- suppressor gene APC (or other) 4
Figure 18.25
Colon 1
Loss of tumor- suppressor gene APC (or other) 4
Loss of tumor- suppressor gene p53 2
Activation of ras oncogene 3
Loss of tumor- suppressor gene DCC
Additional mutations 5
Colon wall
Figure A multistep model for the development of colorectal cancer.
Normal colon epithelial cells
Small benign growth (polyp)
Larger benign growth (adenoma)
Malignant tumor (carcinoma)

39. Inherited Predisposition and Other Factors Contributing to Cancer
Individuals can inherit oncogenes or mutant alleles of tumor-suppressor genes
Inherited mutations in the tumor-suppressor gene adenomatous polyposis coli are common in individuals with colorectal cancer
Mutations in the BRCA1 or BRCA2 gene are found in at least half of inherited breast cancers, and tests using DNA sequencing can detect these mutations
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40. Active repressor: corepressor bound
Figure 18.UN02
Genes expressed
Genes not expressed
Promoter
Genes
Operator
Active repressor: corepressor bound
Inactive repressor: no corepressor present
Corepressor
Figure 18.UN02 Summary figure, Concept 18.1

41. Active repressor: no inducer present Inactive repressor: inducer bound
Figure 18.UN03
Genes not expressed
Genes expressed
Promoter
Operator
Genes
Active repressor: no inducer present
Inactive repressor: inducer bound
Figure 18.UN03 Summary figure, Concept 18.1

42. Enhancer for liver-specific genes Enhancer for lens-specific genes
Figure 18.UN04a
Chromatin modification
Transcription
• Genes in highly compacted chromatin are generally not transcribed.
• Regulation of transcription initiation: DNA control elements in enhancers bind specific transcription factors.
• Histone acetylation seems to loosen chromatin structure, enhancing transcription.
Bending of the DNA enables activators to contact proteins at the promoter, initiating transcription.
• DNA methylation generally reduces transcription.
• Coordinate regulation:
Enhancer for liver-specific genes
Enhancer for lens-specific genes
Chromatin modification
Figure 18.UN04a Summary figure, Concept 18.2 (part 1)
Transcription
RNA processing
• Alternative RNA splicing:
RNA processing
Primary RNA transcript
mRNA degradation
Translation
mRNA or
Protein processing and degradation

43. Protein processing and degradation
Figure 18.UN04b
Chromatin modification
Transcription
RNA processing
mRNA degradation
Translation
Protein processing and degradation
Translation
• Initiation of translation can be controlled via regulation of initiation factors.
Figure 18.UN04b Summary figure, Concept 18.2 (part 2)
mRNA degradation
• Each mRNA has a characteristic life span, determined in part by sequences in the 5 and 3 UTRs.
Protein processing and degradation
• Protein processing and degradation by proteasomes are subject to regulation.

44. Protein processing and degradation
Figure 18.UN05
Chromatin modification
• Small or large noncoding RNAs can promote the formation of heterochromatin in certain regions, blocking transcription.
Chromatin modification
Transcription
Translation
RNA processing
• miRNA or siRNA can block the translation of specific mRNAs.
mRNA degradation
Translation
Protein processing and degradation
Figure 18.UN05 Summary figure, Concept 18.3
mRNA degradation
• miRNA or siRNA can target specific mRNAs for destruction.