Download Differential Gene Expression in Development

19
Differential Gene Expression
in Development
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?
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.
Figure 19.1 From Fertilized Egg to Adult (Part 1)
Figure 19.1 From Fertilized Egg to Adult (Part 2)
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.
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.
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.
19.1 What Are the Processes of Development?
A cell’s 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.
Figure 19.2 Developmental Potential in Early Frog Embryos (Part 1)
Figure 19.2 Developmental Potential in Early Frog Embryos (Part 2)
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.
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.
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
plant—a clone.
This ability is exploited in agricultural
biotechnology.
Figure 19.3 Cloning a Plant
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.
19.2 Is Cell Differentiation Irreversible?
These experiments indicate that:
• No genetic information is lost as the cell
passes through developmental stages—
called genomic equivalence.
• The cytoplasmic environment can
modify the cell’s fate.
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 mother’s
uterus.
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.
Figure 19.4 Cloning a Mammal (Part 1)
Figure 19.4 Cloning a Mammal (Part 2)
19.2 Is Cell Differentiation Irreversible?
One goal of the sheep cloning was to
develop ways to produce transgenic
sheep—for example in “pharming.”
Many mammals have now been cloned—
mice, goats, cattle, horses.
Cloning may help to preserve some
endangered animal species.
Figure 19.5 Cloned Mice
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.
19.2 Is Cell Differentiation Irreversible?
In plants, growing regions contain
meristems—clusters 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.
19.2 Is Cell Differentiation Irreversible?
In mammals, stem cells occur in tissues
that require frequent replacement—skin,
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.
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.
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.
Figure 19.6 Repairing a Damaged Heart
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.
Figure 19.7 The Potential Use of Embryonic Stem Cells in Medicine (Part 1)
Figure 19.7 The Potential Use of Embryonic Stem Cells in Medicine (Part 2)
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 mother’s uterus.
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
patient’s own nuclei.
Figure 19.8 Therapeutic Cloning (Part 1)
Figure 19.8 Therapeutic Cloning (Part 2)
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.
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 muscledetermining genes and acts as its own
promoter to keep levels high.
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.
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.
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
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.
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.
Figure 19.9 Asymmetry in the Early Sea Urchin Embryo (Part 1)
Figure 19.9 Asymmetry in the Early Sea Urchin Embryo (Part 2)
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.
Figure 19.10 The Principle of Cytoplasmic Segregation
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.
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.
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.
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 won’t develop.
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.
Figure 19.11 Embryonic Inducers in the Vertebrate Eye
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.
Figure 19.12 Induction during Vulval Development in Caenorhabditis elegans (A)
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 signals—the
primary and secondary inducers.
Figure 19.12 Induction during Vulval Development in Caenorhabditis elegans (B)
19.4 How Is Cell Fate Determined?
Anchor cell produces primary inducer—
cells that receive it become vulval
precursor cells. Other cells become
epidermis.
Cell closest to anchor cell becomes the
primary vulval precursor—produces the
secondary inducer.
The inducers control activation or
inactivation of genes through signal
transduction cascades.
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).
Figure 19.13 Embryonic Induction
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 death—apoptosis—is
also important.
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.
Figure 19.14 Apoptosis Removes the Tissue between Human Fingers
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.
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.
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.
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.
Figure 19.15 Organ Identity Genes in Arabidopsis Flowers (A)
19.5 How Does Gene Expression Determine Pattern Formation?
Two lines of experimental evidence
support this model:
Loss-of-function mutations—mutation in
A results in no sepals or petals.
Gain-of-function mutations—promoter for
C can be coupled to A—result is only
sepals and petals.
Figure 19.15 Organ Identity Genes in Arabidopsis Flowers (B)
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.
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.
Figure 19.16 A Nonflowering Mutant
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.
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.
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.
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 factors—a transcriptional
cascade.
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 anteriorposterior 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.
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.
Figure 19.17 Bicoid Protein Provides Positional Information
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.
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.
Figure 19.18 A Gene Cascade Controls Pattern Formation in the Drosophila Embryo
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.
Figure 19.19 Hox Genes in Drosophila
19.5 How Does Gene Expression Determine Pattern Formation?
Clues to hox gene function came from
homeotic mutants.
Antennapedia mutation—legs grow in
place of antennae
Bithorax mutation—an extra pair of wings
grow
Figure 19.20 A Homeotic Mutation in Drosophila
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 DNA—
called the homeodomain.
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.