Differential Gene Expression in Development
Differential Gene Expression in Development
The Processes of Development
The Role of Differential Gene Expression in Cell Differentiation
The Roles of Cytoplasmic Segregation and Induction in Cell Determination
The Role of ________ Formation in Organ Development
The Role of Differential Gene Expression in Establishing Body Segmentation
The Processes of Development
Development is a series of progressive changes in shape, form, and function
that occur during an organism's life cycle.
The earliest stage is called the ________ stage.
Embryos typically acquire food directly or indirectly from a parent.
Embryonic stages precede birth, and development continues until death.
The Processes of Development
Development consists of growth, differentiation, and morphogenesis.
Growth occurs by cell division and/or expansion.
Repeated mitotic cell divisions increase cell number.
Plants use cell elongation to increase size early in development.
An animal embryo may consist of thousands of cells before it becomes ________
The Processes of Development
Differentiation is the process in which cells become specialized structurally
and functionally.
When the embryo is small, each cell has the potential to develop in many
different ways.
As development proceeds, the possibilities available to individual cells
narrow, until each cell's fate is ________ and the cell has differentiated.
The Processes of Development
Morphogenesis is the shaping of the multicellular body and its organs.
Morphogenesis results from ________ formation, the organization of ________
tissues into specific structures.
In plants, movement of cells is limited, because cell walls adhere to each
other and restrict movement.
Animal cells can move, which is important during________
Programmed cell death is essential in the orderly development of both plant
and animals.
The Processes of Development
Staining early embryo cells can produce fate maps revealing which adult
structures derive from which part of the embryo.
Moving a section of cells from a region of an early frog embryo to another
region causes the cells to differentiate appropriately for the newnot the
oldlocation.
The Processes of Development
Cells do not generally maintain this developmental plasticity.
Later in development, transplanted tissue from an embryo develops into the
original type of tissue, regardless of its new location. At this point the cells
are said to be determined.
Determination is the commitment of a cell to a particular fate and is
influenced by the extracellular environment and cell contents acting on the
cell's genome.
Determination is followed by differentiation.
The Role of Differential Gene
Expression in Cell Differentiation
Differentiation results from differential gene expression.
The fertilized egg is a ________ cell. That is, it can give rise to all other
cell types of the organism.
As development proceeds, cells lose their totipotency and become determined,
and then differentiate.
The Role of Differential Gene
Expression in Cell Differentiation
In some cases, ________ is irreversible.
Red blood cells lose their nuclei as they mature.
Tracheid cells die before they become functional water-transporting
structures.
In both, the absence of a functional nucleus explains their irreversibility.
The Role of Differential Gene
Expression in Cell Differentiation
Sometimes differentiation is reversible.
In general, differentiation in plant cells can be reversed more easily than
differentiation in animal cells.
A carrot root cell can be ________ into forming a whole new plant.
The new plant is called a clone, because it is genetically identical to the
original plant.
The ability to generate an entire plant from a single cell is invaluable to
biotechnology.
The Role of Differential Gene
Expression in Cell Differentiation
Nuclear transplant experiments have shown that somatic cells contain the
entire genome.
When the nucleus of an unfertilized frog egg is replaced with the nucleus of a
somatic cell from an early frog zygote, normal early embryos develop.
These experiments led to two important conclusions:
§ No information is lost in the early stages of embryonic development (a
principle known as genomic________
§ The cytoplasmic environment around a nucleus can modify its fate.
The Role of Differential Gene
Expression in Cell Differentiation
In humans, the ________ of early embryonic cells permits genetic screening and
in vitro fertilization:
§ A single cell is removed from an 8-cell human embryo.
§ The cell is tested for harmful genetic conditions.
§ Each remaining cell, being totipotent, can be stimulated to divide and form a
normal embryo.
The Role of Differential Gene
Expression in Cell Differentiation
In 1997, Ian Wilmut and colleagues starved sheep cells of nutrients, which
arrested them in the G1 phase.
These cells were fused with enucleated eggs from a different ewe and
stimulated to enter the S phase.
The early embryos were transplanted to the womb of a surrogate mother ewe. One
lamb, named Dolly, survived to birth.
The ultimate goal of sheep ________ is to develop transgenic (genetically
modified) ewes that can produce drugs in their milk.
The Role of Differential Gene
Expression in Cell Differentiation
Other mammals, including mice, cows, and goats, have been cloned by starving
donor cells.
Cloning is being done to preserve rare breeds and endangered species.
Goats have been genetically engineered to produce useful proteins in their
milk.
The Role of Differential Gene
Expression in Cell Differentiation
A human tumor called a teratocarcinoma is an example of nuclear totipotency
gone awry.
In this type of tumor, a differentiated cell reverts to an undifferentiated
stage and starts dividing, forming a tumor.
Some cells in the tumor differentiate, forming kidney tubes, hair, or even
teeth.
The Role of Differential Gene
Expression in Cell Differentiation
Stem cells are ________ dividing cells that are found even in adults.
A few examples are those found in bone marrow, skin, and intestine, tissues
which need frequent cell replacement.
In the body, stem cells have a limited ability to differentiate, but by
manipulating the environment, stem cells can be made to differentiate.
The Role of Differential Gene
Expression in Cell Differentiation
An example of a stem cell differentiation in response to altered environmental
signals in mice:
§ Brain stem cells were transplanted to bone marrow, where they became bone
marrow stem cells and produced blood cells.
§ The brain stem cells normally differentiate into nerve cells.
§ The reverse experiment resulted in bone marrow cells that differentiated into
brain cells.
The Role of Differential GeneExpression in Cell Differentiation
Stem cells with the greatest totipotency are the cells of early embryos.
Stem cells can be removed from embryos and grown in the lab. They can be
induced to differentiate using certain signal molecules.
Treatment of mouse embryonic stem cells with a derivative of vitamin A causes
them to form nerve cells. Other ________ factors induce them to form blood
cells.
In the future, manipulation and customizing of embryonic cells in culture may
make new disease treatments possible.
The Role of Differential Gene
Expression in Cell Differentiation
If embryonic stem cells are used to form tissues for a transplantation,
genetic differences between the donor and recipient may result in rejection of
the transplant.
A procedure called therapeutic cloning has been proposed to address this
problem.
This process involves fusing a cell nucleus from the recipient with an
enucleated egg cell from a female donor.
These cells can be induced to differentiate into the desired tissue for
transplantation without the risk of immune system rejection.
The Role of Differential Gene
Expression in Cell Differentiation
There appears to be genome constancy or equivalence in all somatic cells.
To understand what determines differential gene expression, myoblasts,
precursors to muscle cells, have been studied.
MyoD1 is the first gene switched on and it codes for a helix-loop-helix type
transcription factor (MyoD1), a DNA-binding protein.
MyoD1 protein binds to the promoters of muscle-specific genes, switching them
on.
It also binds to its own promoter, keeping itself in the myoblasts and their
descendants.
The Roles of Cytoplasmic Segregation
and Induction in Cell Determination
Chemical signals are involved in cell differentiation.
Two overall mechanisms for producing these signals have been found:
§ Cytoplasmic ________ occurs when a factor is unequally distributed in the
zygote and ends up in some daughter cells but not others.
§ Induction occurs when a factor is produced and secreted by some cells to
induce other cells to differentiate.
The Roles of Cytoplasmic Segregation
and Induction in Cell Determination
Polarity is an early event in development.
Polarity includes the establishment of the most obvious differentiation, such
as anteriorposterior ends and dorsalventral surfaces.
When the egg divides, the resulting cells receive unequal amounts of materials
that were distributed unevenly in the cytoplasm of the zygote.
These differences in cytoplasmic makeup account for some of the earliest
differentiation in embryos.
The Roles of Cytoplasmic Segregation
and Induction in Cell Determination
An example of induction is the development of vertebrate eyes.
The developing forebrain bulges out at both sides, forming optic vesicles.
Signals from the optic vesicles induce the surface tissue to form the lens
placodes, which differentiate into lenses.
The developing lens influences the size of the optic cup, and also induces the
surface tissue to develop into the cornea.
The Roles of Cytoplasmic Segregation
and Induction in Cell Determination
The development of the nematode Caenorhabditis elegans has been studied
extensively.
Development from egg to larva takes just 8 hours and the adult stage is
reached in 3.5 days.
Development can be observed easily under low magnification because the body
covering is transparent.
The source of each of the 959 somatic cells of the adult form have been
identified.
The Roles of Cytoplasmic Segregation
and Induction in Cell Determination
During development of C. elegans, the anchor cell induces the vulva to form.
The anchor cell controls the fates of six cells on the ventral surface through
two molecular switches.
Each of the six cells has three possible fates: it could become a primary
vulval precursor, a secondary vulval precursor, or an epidermal cell.
The anchor cell produces an inducer, which controls specific genes in
responding cells.
The Roles of Cytoplasmic Segregation
and Induction in Cell Determination
Much of development is controlled by molecular switches that allow a cell to
take one of two alternative tracks.
The challenge is to find these molecular switches and determine how they work.
The Role of Pattern Formation
in Organ Development
Pattern formation is the spatial organization of a tissue or organism.
It is inextricably linked to morphogenesis, the appearance of body form.
The Role of Pattern Formation
in Organ Development
________ is programmed cell death.
It is caused by the activation of "death" genes.
Of the 1,090 somatic cells produced by C. elegans, 131 cells are programmed to
die.
The genes ced-4 and ced-3 appear to control this process.
A third gene, ced-9, codes for an inhibitor of ced-4. Therefore, when cell
death is required, ced-3 and ced-4 are active and ced-9 is inactive.
The Role of Pattern Formation
in Organ Development
Early human embryos have ________ between fingers and toes.
Between day 41 and day 56, the cells of the webbing die, freeing individual
fingers and toes.
The enzyme caspase stimulates apoptosis and is homologous to ced-3.
The protein in humans that inhibits apoptosis is bcl-2, which is similar to
the protein encoded by the C. elegans gene ced-9.
One form of cancer, follicular large-cell lymphoma, is caused by
overexpression of bcl-2 in some white blood cells.
The Role of Pattern Formation
in Organ Development
The identity of the whorls from which floral organs develop is determined by a
group of genes.
These genes have been best described in Arabidopsis thaliana.
This plant has a small genome, produces many seeds, develops rapidly and it is
easy to produce mutations.
Normal Arabidopsis flowers have four whorls of organs. Homeotic mutants have
the wrong organs in particular whorls.
The Role of Pattern Formation
in Organ Development
Cells in the meristem differentiate to form the whorls through the expression
of three organ identity genes.
Whorl 1 expresses gene A; whorl 2 expresses genes A and B; whorl 3 expresses
genes B and C; and whorl 4 expresses gene C.
The products of these genes are transcription factors that form dimers.
The composition of the dimer determines which other genes will be activated by
the transcription factor.
This is called combinatorial gene regulation.
The Role of Pattern Formation
in Organ Development
Many transcription factors, including the A, B, and C proteins, have a
DNA-binding domain called the MADS box.
A gene called leafy controls the transcription of the ABC genes.
Plants with a mutation that causes the underexpression of this gene make
leaves but no flowers.
The Role of Pattern Formation
in Organ Development
Certain cells in both plants and animals seem to "know" where they are within
the organism. This is called positional information.
Positional information usually comes in the form of a signal created by
the________ ________ of a morphogen.
There are two requirements for a signal to be considered a morphogen.
§ It must directly affect target cells.
§ Different concentrations of the signal must cause different effects.
The Role of Pattern Formation
in Organ Development
A vertebrate limb develops from a round bud.
The cells that become the bones and muscles of the limb must receive
positional information, then organize to shape properly.
A group of cells at the posterior base of the bud makes a morphogen called
BMP2, whose gradient determines the anteriorposterior axis of the limb.
Cells that get the highest dose of BMP2 make the thumb, and the smallest dose
results in the little finger.
The Role of Differential Gene Expression
in Establishing Body Segmentation
The adult Drosophila has different types of body segments:
§ The head is composed of several fused segments. There are three different
thoracic segments, and eight abdominal segments.
§ The 13 seemingly identical segments of the Drosophila larva correspond to the
specialized adult segments.
§ The process of differentiation begins with establishing the polarity of the
embryo.
The Role of Differential Gene Expression
in Establishing Body Segmentation
In Drosophila, unequal distribution of morphogens helps establish the basic
coordinates.
The morphogen molecules are products of specific maternal effect genes
distributed by the mother to the eggs.
The maternal effect genes are transcribed in the ovarian cells that surround
the developing egg.
It is their influence that determines the ________ and ________ axes of the
embryo.
Two maternal effect genes are bicoid, which controls anterior larval
development, and nanos, which controls posterior larval development.
The Role of Differential Gene Expression
in Establishing Body Segmentation
Segmentation genes influence the number, boundaries, and ________ of the body
segments.
Three classes of segmentation genes act one after another:
§ Gap genes organize large areas along the anteriorposterior axis.
§ Pair rule genes divide the embryo into units of two segments each.
§ Segment polarity genes determine the boundaries of anterior-posterior
segments.
Finally, homeotic genes are expressed along the length of the body and tell
the segments what to become.
The Role of Differential Gene Expression
in Establishing Body Segmentation
Development is the result of a sequence of changes, each one triggering the
next.
The unfertilized egg has stored mRNA that supports protein synthesis during
early development.
Cytoplasmic segregation of the stored mRNA provides positional information.
mRNA for Bicoid protein is localized at the end of the egg destined to become
the anterior end of the fly.
The Role of Differential Gene Expression
in Establishing Body Segmentation
The Bicoid and Nanos proteins regulate the expression of the gap genes.
Bicoid affects transcription, Nanos affects translation.
High Bicoid at the anterior turns on a gap gene (hunchback), while
simultaneously turning off another gap gene (Krόppel).
Nanos at the posterior reduces hunchback.
The gap genes control the expression of pair rule genes.
The pair rule gene products control the segmentation polarity genes.
The Role of Differential Gene Expression
in Establishing Body Segmentation
The homeotic genes specify the properties of each segment. Mutations in these
genes produce changes in segment identity.
One homeotic gene mutant (Antennapedia) causes legs to grow in the place of
antennae. Bithorax causes an extra pair of wings to grow.
Antennapedia and bithorax are mutations of adjacent gene clusters.
The genes in these clusters are arranged on the chromosome in the same order
as the segments they determine.
The Role of Differential Gene Expression
in Establishing Body Segmentation
A 180-base-pair DNA sequence that is common to the Antennapedia and bithorax
homeotic genes is called the homeobox.
It codes for a 60-amino-acid sequence called the homeodomain, which binds DNA.
The homeodomain has the helix-turn-helix motif.
Each homeodomain recognizes a specific DNA sequence.
Homeotic genes code for transcription factors.
Video 19.1 From egg to tadpole: Embryonic development in a frog, Xenopus
Video 19.2 Embryogenesis of a nematode worm, C. elegans
Video 19.3 Embryonic development in two zebrafish
Video 19.4 Blood vessel development
Animation 19.1 Embryonic Stem Cells
Animation 19.2 Early Asymmetry in the Embryo
Animation 19.3 Pattern Formation in the Drosophila Embryo