Differential Gene Expression in Development

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Differential Gene Expression in Development
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19 Differential Gene Expression in Development

• 19.1 What Are the Processes of Development?
• 19.2 Is Cell Differentiation Irreversible?
• 19.3 What Is the Role of Gene Expression in Cell
  Differentiation?
• 19.4 How Is Cell Fate Determined?
• 19.5 How Does Gene Expression Determine Pattern
  Formation?

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19.1 What Are the Processes of Development?

• Development the process in which a multicellular
  organism undergoes a series of progressive
  changes that characterizes its life cycle.
• In its earliest stages, a plant or animal is
  called an embryo.
• The embryo can be protected in a seed, an egg
  shell, or a uterus.

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Figure 19.1 From Fertilized Egg to Adult (Part 1)
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Figure 19.1 From Fertilized Egg to Adult (Part 2)
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19.1 What Are the Processes of Development?

• Four processes of development
• Determination sets the fate of the cell.
• Differentiation is the process by which different
  types of cells arise.
• Morphogenesis shapes differentiated cells into
  organs, etc.
• Growth is an increase in body size by cell
  division and cell expansion.

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19.1 What Are the Processes of Development?

• Cells in a multicellular organisms are
  genetically identical they differ from one
  another because of differential gene expression.
• In early embryos, every cell has potential to
  develop in many different ways.

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19.1 What Are the Processes of Development?

• Morphogenesis in plant cells results from
  organized division and expansion of cells.
• In animals, cell movements are important in
  morphogenesis.
• Apoptosis (programmed cell death) is also
  important in orderly development.

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19.1 What Are the Processes of Development?

• A cells fate, the type of cell it will
  ultimately become, is a function of differential
  gene expression and morphogenesis.
• Experiments in which specific cells of an early
  embryo are grafted to new positions on another
  embryo show the role of morphogenesis.

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Figure 19.2 Developmental Potential in Early Frog
Embryos (Part 1)
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Figure 19.2 Developmental Potential in Early Frog
Embryos (Part 2)
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19.1 What Are the Processes of Development?

• Early embryonic cells have a range of possible
  fates, but possibilities become more restricted
  as development proceeds.
• The extracellular environment, as well as the
  cell contents, influence the genome and
  differentiation.

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19.2 Is Cell Differentiation Irreversible?

• A zygote is totipotent, it can give rise to every
  cell type in the adult body.
• Later in development, the cells lose totipotency
  and become determined.
• Determination is followed by differentiation.
• But most cells retain the entire genome, and have
  the capacity for totipotency.

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19.2 Is Cell Differentiation Irreversible?

• Plant cells are usually totipotent.
• Differentiated cells can be removed from a plant
  and grown in a culture, and eventually form a
  genetically identical planta clone.
• This ability is exploited in agricultural
  biotechnology.

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Figure 19.3 Cloning a Plant
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19.2 Is Cell Differentiation Irreversible?

• Animal somatic cells can also retain their
  totipotency.
• Experimental fusion of later embryo cells or
  nuclei with enucleated eggs stimulates cell
  division and development into normal adults.

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19.2 Is Cell Differentiation Irreversible?

• These experiments indicate that
• No genetic information is lost as the cell passes
  through developmental stagescalled genomic
  equivalence.
• The cytoplasmic environment can modify the cells
  fate.

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19.2 Is Cell Differentiation Irreversible?

• Totipotency of early embryonic cells is used in
  assisted reproductive technologies.
• The 8-cell embryo can be isolated, and one cell
  removed to test for harmful genetic conditions.
  The cells are then stimulated to divide to form
  an embryo and are implanted into the mothers
  uterus.

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19.2 Is Cell Differentiation Irreversible?

• Adult somatic cells also retain totipotency.
• The cell fusion technique was used to clone a
  sheep in the 1990s.
• The cells used in the experiments were starved
  for one week to arrest them in the G1 phase of
  the cell cycle.

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Figure 19.4 Cloning a Mammal (Part 1)
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Figure 19.4 Cloning a Mammal (Part 2)
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19.2 Is Cell Differentiation Irreversible?

• One goal of the sheep cloning was to develop ways
  to produce transgenic sheepfor example in
  pharming.
• Many mammals have now been clonedmice, goats,
  cattle, horses.
• Cloning may help to preserve some endangered
  animal species.

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Figure 19.5 Cloned Mice
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19.2 Is Cell Differentiation Irreversible?

• Differentiated cells stay differentiated because
  of their environment and developmental history.
• In normal development, a complex series of timed
  signals results in patterns of differentiation
  that result in the mature organism.

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19.2 Is Cell Differentiation Irreversible?

• In plants, growing regions contain
  meristemsclusters of undifferentiated cells that
  can give rise to specialized structures such as
  roots and stems.
• Plants have fewer cell types than animals, and
  differ mostly in the structure of the cell walls.

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19.2 Is Cell Differentiation Irreversible?

• In mammals, stem cells occur in tissues that
  require frequent replacementskin, blood,
  intestinal lining.
• Stem cells produce daughter cells that
  differentiate into several cell types. Not
  totipotent, but pluripotent.
• Differentiation of pluripotent stem cells occurs
  as needed.

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19.2 Is Cell Differentiation Irreversible?

• Bone marrow transplantation is used in cancer
  therapies.
• Therapies that kill cancer cells can also kill
  other rapidly dividing cells such as bone marrow
  stem cells.
• The stem cells are removed during the therapy,
  and then returned to the bone marrow.

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19.2 Is Cell Differentiation Irreversible?

• Adjacent cells can influence stem cell
  differentiation.
• If bone marrow stem cells that can form muscle
  are transplanted to the heart, they form muscle.
  This has been used in animals to repair a damaged
  heart.

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Figure 19.6 Repairing a Damaged Heart
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19.2 Is Cell Differentiation Irreversible?

• Totipotent stem cells are found only in early
  embryos.
• Cells can be removed from embryos and grown
  indefinitely.
• These cells can be stimulated to differentiate
  with appropriate signals. For example, a
  derivative of vitamin A causes them to form
  neurons.

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Figure 19.7 The Potential Use of Embryonic Stem
Cells in Medicine (Part 1)
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Figure 19.7 The Potential Use of Embryonic Stem
Cells in Medicine (Part 2)
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19.2 Is Cell Differentiation Irreversible?

• There is a potential to use human embryonic stem
  cells in medical applications.
• Human embryos are produced by in vitro
  fertilization, and only a few are implanted into
  the mothers uterus.

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19.2 Is Cell Differentiation Irreversible?

• Tissues from embryonic stem cells could be
  rejected by recipients because T cells would
  recognize them as nonself.
• Therapeutic cloning would involve nuclear
  transplantation and stem cell implantation
  combined.
• Stem cells would be derived from an embryo after
  being implanted with the patients own nuclei.

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Figure 19.8 Therapeutic Cloning (Part 1)
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Figure 19.8 Therapeutic Cloning (Part 2)
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19.3 What Is the Role of Gene Expression in Cell
Differentiation?

• Major controls of gene expression in
  differentiation are transcriptional controls.
• While all cells in an organism have the same DNA,
  it can be demonstrated with nucleic acid
  hybridization that differentiated cells have
  different mRNAs.

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19.3 What Is the Role of Gene Expression in Cell
Differentiation?

• Myoblasts are undifferentiated precursors to
  muscle cells.
• Expression of a gene called MyoD produces a
  transcription factor MyoD.
• MyoD binds to promoters of muscle-determining
  genes and acts as its own promoter to keep levels
  high.

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19.3 What Is the Role of Gene Expression in Cell
Differentiation?

• If MyoD is transfected into other cell
  precursors, they also become muscle cells.
• Genes such as MyoD that encode for transcription
  factors fundamental to development are called
  developmental genes.

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19.3 What Is the Role of Gene Expression in Cell
Differentiation?

• Determination and differentiation are carried out
  by complex interactions between many genes and
  their products.
• Researchers using the sea urchin estimate that
  1/3 of the eukaryotic genome is used only during
  development.

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19.4 How Is Cell Fate Determined?

• Transcriptional controls that lead to
  differentiation are stimulated by chemical
  signals.
• Two mechanisms to produce the signals
• Cytoplasmic segregation
• Induction

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19.4 How Is Cell Fate Determined?

• Cytoplasmic segregation
• Some patterns of gene expression are under
  cytoplasmic control.
• Polarity having a top and a bottom. It can
  develop even in the zygote the animal pole is
  the top, the vegetal pole is the bottom.
• Yolk and other factors can be distributed
  asymmetrically.

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19.4 How Is Cell Fate Determined?

• Polarity was demonstrated using sea urchin
  embryos.
• If an 8-cell embryo is cut vertically, it
  develops into two small larvae.
• If the 8-cell embryo is cut horizontally, the
  bottom develops into a larva, the top remains
  embryonic.

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Figure 19.9 Asymmetry in the Early Sea Urchin
Embryo (Part 1)
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Figure 19.9 Asymmetry in the Early Sea Urchin
Embryo (Part 2)
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19.4 How Is Cell Fate Determined?

• Cytoplasmic determinants are distributed
  unequally in the egg cytoplasm.
• These materials play a role in development of
  many animals.

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Figure 19.10 The Principle of Cytoplasmic
Segregation
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19.4 How Is Cell Fate Determined?

• The cytoskeleton contributes to distribution of
  cytoplasmic determinants.
• Microtubules and microfilaments have polarity,
  and cytoskeletal elements can bind certain
  proteins.
• In sea urchin eggs, a protein binds to the
  growing end () of a microfilament and to an mRNA
  encoding a cytoplasmic determinant.

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19.4 How Is Cell Fate Determined?

• As microfilament grows toward one end of the
  cell, it pulls the mRNA along.
• The unequal distribution of mRNA results in
  unequal distribution of the protein it encodes.

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19.4 How Is Cell Fate Determined?

• Induction
• Fates of particular cells and tissues are
  sometimes determined by interactions with other
  tissues. Mediated by chemical signals and signal
  transduction pathways.

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19.4 How Is Cell Fate Determined?

• Development of the lens in the vertebrate eye
• The forebrain bulges out to form optic vesicles,
  which come in contact with cells at the surface
  of the head. These surface cells ultimately
  become the lens.
• The optic vesicle must contact the surface cells,
  or the lens wont develop.

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19.4 How Is Cell Fate Determined?

• The surface cells receive a signal, or inducer,
  from the optic vesicles.
• The developing lens also induces surface cells
  covering it to develop into the cornea.

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Figure 19.11 Embryonic Inducers in the Vertebrate
Eye
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19.4 How Is Cell Fate Determined?

• Vulval development in Caenorhabditis elegans
• Adult C. elegans has 959 somatic cells the
  source of each cell has been determined.
• Adults are hermaphroditic eggs are laid through
  a ventral pore called the vulva.

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Figure 19.12 Induction during Vulval Development
in Caenorhabditis elegans (A)
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19.4 How Is Cell Fate Determined?

• During development, a single cell, the anchor
  cell, induces the vulva to form.
• If the anchor cell is destroyed, the vulva does
  not form.
• Anchor cell controls fate of six cells on the
  ventral surface by two signalsthe primary and
  secondary inducers.

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Figure 19.12 Induction during Vulval Development
in Caenorhabditis elegans (B)
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19.4 How Is Cell Fate Determined?

• Anchor cell produces primary inducercells that
  receive it become vulval precursor cells. Other
  cells become epidermis.
• Cell closest to anchor cell becomes the primary
  vulval precursorproduces the secondary inducer.
• The inducers control activation or inactivation
  of genes through signal transduction cascades.

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19.4 How Is Cell Fate Determined?

• Much of development is controlled by such
  molecular switches, that allow a cell to follow
  one of two alternative tracks.
• Primary inducer released by the anchor cell is
  homologous to a human growth factor called EGF
  (epidermal growth factor).

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Figure 19.13 Embryonic Induction
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19.5 How Does Gene Expression Determine Pattern
Formation?

• Pattern formation the process that results in
  the spatial organization of tissues.
• Linked with morphogenesis.
• Programmed cell deathapoptosisis also
  important.

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19.5 How Does Gene Expression Determine Pattern
Formation?

• Apoptosis can sculpt organs such as the hands
  during development.
• Connective tissue links fingers in early human
  embryo. The connective cells die later, freeing
  the fingers.

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Figure 19.14 Apoptosis Removes the Tissue between
Human Fingers
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19.5 How Does Gene Expression Determine Pattern
Formation?

• C. elegans produces exactly 1,090 somatic cells
  as it develops, but 131 of those cells die.
• The sequential expression of two genes control
  this cell death.
• A third gene codes for an inhibitor of apoptosis.

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19.5 How Does Gene Expression Determine Pattern
Formation?

• A similar system acts in humans
• Caspases that stimulate apoptosis, are similar to
  proteins encoded by the nematode genes, as is the
  inhibitor of apoptosis.

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19.5 How Does Gene Expression Determine Pattern
Formation?

• Flowers are composed of organs (sepals, petals,
  stamens, carpels) arranged around a central axis
  in whorls.
• The whorls develop from meristems
  (undifferentiated cells)organ identity is
  determined by organ identity genes.

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19.5 How Does Gene Expression Determine Pattern
Formation?

• Organ identity genes have been studied in
  Arabidopsis.
• Three classes of organ identity genes
• Class A, expressed in sepals and petals.
• Class B, expressed in petals and stamens.
• Class C, expressed in stamens and carpels.

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Figure 19.15 Organ Identity Genes in Arabidopsis
Flowers (A)
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19.5 How Does Gene Expression Determine Pattern
Formation?

• Two lines of experimental evidence support this
  model
• Loss-of-function mutationsmutation in A results
  in no sepals or petals.
• Gain-of-function mutationspromoter for C can be
  coupled to Aresult is only sepals and petals.

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Figure 19.15 Organ Identity Genes in Arabidopsis
Flowers (B)
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19.5 How Does Gene Expression Determine Pattern
Formation?

• Gene classes A, B, and C code for subunits of
  transcription factors, which are active as
  dimers.
• Gene regulation is combinatorial.
• A common feature of the transcription factors is
  a DNA-binding domain called the MADS box.
• They also have domains that can bind to other
  proteins in a transcription initiation complex.

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19.5 How Does Gene Expression Determine Pattern
Formation?

• A gene called leafy codes for a protein that
  controls transcription of organ identity genes.
• Plants with a mutation that causes
  underexpression of leafy do not produce flowers.
• Protein product of this gene acts as a
  transcription factor to stimulate gene classes A,
  B, and C.

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Figure 19.16 A Nonflowering Mutant
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19.5 How Does Gene Expression Determine Pattern
Formation?

• Fate of a cell is often determined by where the
  cell is.
• Positional information comes in the form a
  signal, a morphogen, that diffuses down a body
  axis, setting up a concentration gradient.

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19.5 How Does Gene Expression Determine Pattern
Formation?

• A morphogen must directly affect target cells,
  and different concentrations of the morphogen
  result in different effects.
• Example development of a vertebrate limb.
• Cells in the developing limb bud that become bone
  and muscle must receive positional information.

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19.5 How Does Gene Expression Determine Pattern
Formation?

• Cells at the posterior base of the limb bud,
  called the zone of polarizing activity, make a
  morphogen called BMP2.
• The gradient of BMP2 determines the
  posterior-anterior axis of the developing limb.
• Cells getting the highest dose make the little
  finger, those getting the lowest dose make the
  thumb.

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19.5 How Does Gene Expression Determine Pattern
Formation?

• The fruit fly Drosophila melanogaster has a
  segmented body head, thorax, and abdomen, each
  made of several segments.
• Several types of genes are expressed sequentially
  to define these segments.
• Genes in each step code for transcription factors
  that in turn control synthesis of other
  transcription factorsa transcriptional cascade.

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19.5 How Does Gene Expression Determine Pattern
Formation?

• Maternal effect genes are transcribed in the
  cells of the ovary that surround the anterior
  part of the egg.
• Bicoid and nanos determine the anterior-posterior
  axis. The mRNAs diffuse to the anterior end of
  egg.
• Bicoid mRNA stays in the anterior end, and bicoid
  protein diffuses out, creating a gradient.

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19.5 How Does Gene Expression Determine Pattern
Formation?

• At high concentration, bicoid stimulates
  transcription of the hunchback gene. A gradient
  of that protein establishes the head.
• Nanos mRNA is transported to the posterior end.
  Nanos protein inhibits translation of hunchback.

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Figure 19.17 Bicoid Protein Provides Positional
Information
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19.5 How Does Gene Expression Determine Pattern
Formation?

• Actions of these genes have been determined by
  causing mutations in the genes and from
  experiments in which cytoplasm was transferred
  from one egg to another.
• After egg is fertilized, nuclear division produce
  a multinucleate cell called a syncytium. Bicoid
  and nanos mRNAs are translated and establish
  gradients.

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19.5 How Does Gene Expression Determine Pattern
Formation?

• Segmentation genes determine properties of the
  larval segments.
• Three classes of genes act in sequence
• Gap genes organize broad areas.
• Pair rule genes divide embryo into units of two
  segments each.
• Segment polarity genes determine boundaries and
  anterior-posterior organization in individual
  segments.

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Figure 19.18 A Gene Cascade Controls Pattern
Formation in the Drosophila Embryo
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19.5 How Does Gene Expression Determine Pattern
Formation?

• Hox genes are expressed in different combinations
  along the length of the embryo they determine
  what each segment will become.
• Hox genes map on chromosome 3, in two clusters,
  in the same order as the segments whose functions
  they determine.

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Figure 19.19 Hox Genes in Drosophila
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19.5 How Does Gene Expression Determine Pattern
Formation?

• Clues to hox gene function came from homeotic
  mutants.
• Antennapedia mutationlegs grow in place of
  antennae
• Bithorax mutationan extra pair of wings grow

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Figure 19.20 A Homeotic Mutation in Drosophila
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19.5 How Does Gene Expression Determine Pattern
Formation?

• All the hox genes have a common DNA sequence and
  probably arose from a single gene in an
  unsegmented ancestor.
• The common 180-base pair sequence is called the
  homeobox. It encodes a transcription factor that
  binds DNAcalled the homeodomain.

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19.5 How Does Gene Expression Determine Pattern
Formation?

• Genes containing the homeobox are found in many
  animals, including humans.
• Their role is similar to MADS in plants.