Download Module 4D – Genes and Development Development refers to the

Objective # 19
Module 4D – Genes and Development
„ Development
refers to the changes an
organism goes through from
conception to death.
„ In this module, we will take a brief
look at how genes control the early
development of an organism from
single fertilized egg (zygote) to
complex multicellular organism.
Describe the concept of nuclear
equivalence and explain how different
cell types develop in a multicellular
organism in spite of the phenomenon
of nuclear equivalence.
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Objective 19
Objective 19
„ Nuclear
equivalence:
¾ virtually every cell in a multicellular
organism has descended from the
same original cell by mitosis
¾ therefore, virtually every cell has a
copy of the same genetic information.
„ How
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can different cells develop
different characteristics if they all have
the same genetic information?
¾ Gene regulation – different genes are
active in different cells.
„ The study of development is largely
the study of how different genes are
activated in different cells at different
times.
Objective # 20
„
Objective 20
Explain or define each of the
following developmental processes:
a) formation and storage of cytoplasmic
determinants (“maternal instructions”)
b) cytoplasmic localization
c) commitment or determination
d) cell differentiation
e) cell movement and induction
f) pattern formation
g) expression of homeotic genes
h) morphogensis
i) programmed cell death
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„ Although
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details of development vary
from one organism to the next, most
multicellular organisms develop
according to molecular mechanisms
that are fundamentally similar.
„ In this objective we will examine 9
mechanisms that play an important
role in the development of a wide
variety of different organisms.
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Objective 20 a
Cytoplasmic determinants
Objective 20 b
Cytoplasmic localization
„ Cytoplasmic
localization – in the zygote
of some organisms, different cytoplasmic
determinants are concentrated in
different regions of the cytoplasm.
„ Thus, when the zygote divides, cells
receive different levels of cytoplasmic
determinants. This causes them to
follow different developmental pathways.
„ Cytoplasmic
determinants are
molecules in the cytoplasm that help
regulate gene activity and thereby
control cell development.
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Objective 20 b
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Nucleus
Objective 20 b
Cytoplasmic
determinants
„ This
pattern is found in organisms like
the fruit fly, Drosophila, and is called
mosaic development:
Zygote
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Objective 20 b
When the zygote divides, different cells receive
different concentrations of cytoplasmic
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determinants.
Objective 20 c
Commitment or Determination
„ In
other organisms, by contrast, when
a zygote divides, all cells receive
equivalent levels of cytoplasmic
determinants. In this case,
developmental pathways are
determined by cell-cell interactions.
„ This pattern is found in mammals and
is called regulative development.
„ Complex
multicellular organisms are
composed of many types of cells.
„ The molecular decision to develop into
a particular type of specialized cell is
called determination.
„ Determination may occur long before
the cell actually develops any of its
unique characteristics.
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Objective 20 c
Objective 20 d
Cell Differentiation
„A
cell may become partially committed
to a particular developmental pathway
(e.g. head) before becoming fully
committed (e.g. nose).
„ Experiments with cloning complex
organisms have shown that the
commitment of a cell to a specific
developmental path is reversible.
„ Cell
differentiation is the process
whereby a cell actually develops its
unique set of characteristics.
„ It is triggered by gene regulatory
mechanisms that control which genes
are active and how strongly they are
expressed.
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Objective 20 e
Objective 20 e
Cell Movement and Induction
„ Cells
move mainly by changing their
adhesiveness to other cells and to the
extracellular matrix.
„ Changes in adhesiveness are due to
changes in the composition of cell
adhesion proteins such as cadherins
(which bind cells to other cells) and
integrins (which bind cells to the
extracellular matrix).
„ Cell
Movement refers to the migration
of cells to new locations within the
organism.
„ Cells move during many stages of
animal development, sometimes
traveling great distances before
reaching their final destination.
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Objective 20 e
„ Induction
is when developmental
changes in cells are triggered by
chemicals released by adjacent cells.
„ For example, in vertebrates as the
optic cup develops from the forebrain
it releases chemicals that induce
adjacent ectoderm cells to develop into
the lens of the eye:
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Objective 20 e
some cases, groups of cells called
organizers produce diffusible signal
molecules or morphogens that convey
positional information to other cells.
„ Positional information is conveyed by
the concentration of the morphogen.
The closer the target cell is to the
organizer, the higher the concentration
of the morphogen.
Objective 20 e
„ In
„ Experiments
have shown that a single
morphogen can have different effects
depending on far the target cell is from
the organizer.
„ Although only a few morphogens have
been isolated, this is thought to be a
widespread mechanism for determining
relative position during development:
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Objective 20 f
Pattern Formation
„ Pattern
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formation involves establishing
the overall body plan of an organism so
the various body parts develop in the
correct locations. It depends on the
cells’ abilities to detect and respond to
the positional information that guides
their development.
„ Pattern formation has been most
extensively studied in the fruit fly,
Drosophila.
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Objective 20 f
„ In
Drosophila, diffusion of chemical
inducers produce morphogen gradients
that establish the polarity of the body
(front vs. back) and activate various
developmental genes.
„ These genes, in turn, act to divide the
body into 14 narrow compartments
which become the 14 basic body
segments of the fruit fly:
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Objective 20 g
Expression of Homeotic Genes
Objective 20 g
„ Homeotic
genes were originally
discovered in Drosophila, but they have
since been found in many diverse
organisms including plants and
humans.
„ In Drosophila, after pattern formation
divides the body into segments,
homeotic genes control which body
parts will develop in each segment.
„ Homeotic
genes act as “master
switches” which trigger development
of entire body parts.
„ Each homeotic gene codes for
transcription factors that activate a
block of regulatory genes. The
regulatory genes, in turn, trigger
development of a specific body part.
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Different homeotic genes are activated
in different segments of the Drosophila
embryo
Head
lab pb
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for reproduction or display.
Thorax
Abdomen
A d-B
Dfd Scr Antp Ubx abd- ab
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Objective 20 g
„ Mutations
in homeotic genes can lead
to the development of perfectly
normal body parts in unusual places.
„ For example, one homeotic mutation
in Drosophila leads to the development
of a second thoracic segment behind
the first:
Drosophila HOM genes
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Objective 20 h
Morphogenesis
„ Morphogenesis
refers to the
development of overall body form and
structure.
„ Morphogenesis results from the
changes in number, size, structure,
behavior, and location of cells that
occur during development.
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Objective 20 h
Objective 20 i
Programmed Cell Death
„ To
achieve morphogenesis, animals
regulate the following processes:
¾ The number, timing and orientation of
cell division
¾ Cell growth
¾ Changes in cell shape
¾ Cell migration
¾ Cell death
„ In
many organisms, normal
development depends on the
programmed death of certain cells.
„ Cells programmed to die shrivel and
shrink in a process called apoptosis.
„ In contrast, cells that die due to injury
typically swell and burst. This type of
cell death is called necrosis.
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Objective # 21
Objective 20 i
„ An
example of apoptosis is the
programmed death of cells between
the fingers and toes during human
development. If these cells did not
die, you would have paddles instead of
digits.
Describe the processes of
reproductive cloning and
therapeutic cloning.
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Objective 21
Objective 21
„ Although
„ Reproductive
cloning involves making
genetically identical copies of an
organism.
„ This is useful when an organism has
been bred or engineered to have
certain desirable traits and we wish to
produce more genetically identical
copies of the organism.
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many simple organisms
produce clones through asexual
reproduction, more advanced
organisms generally rely on sexual
reproduction where each offspring is
genetically unique.
„ Recently, however, scientists have
developed the ability to clone complex
adult organisms including mammals.
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Wilmut’s Animal Cloning Experiment
Mammary cell is extracted
and grown in nutrientdeficient solution that arrests
the cell cycle.
Wilmut’s Animal Cloning Experiment
Nucleus containing
source DNA
Electric shock opens cell
membranes and triggers
cell division.
After a five-month
pregnancy, a lamb
genetically identical
to the sheep from
which the mammary
Embryo begins to
Embryo is implanted cell was extracted is
develop in vitro.
into surrogate mother. born.
Embryo
Egg cell is extracted.
Mammary cell is inserted
inside covering of egg cell.
Preparation
Nucleus is removed
from egg cell with a
micropipette.
Cell fusion
Development
Cell division
Implantation
Birth of clone
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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
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Objective 21
Objective 21
„ Reproductive
cloning demonstrates
that the nucleus taken from a single
fully differentiated cell can direct the
development of an entire new
organism.
„ This shows that cell determination is
fully reversible.
„ Nevertheless,
reproductive cloning has
some inherent problems:
¾ There is an extremely low success rate.
Only about 3 - 5% of the adult nuclei
transferred to donor eggs result in live
births. In addition, many clones die
soon after birth due to liver failure or
infections.
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Objective 21
Objective 21
¾ These
problems seem to be caused by
genomic imprinting, a process unique to
mammals. During genomic imprinting,
some genes are turned off in the egg cell
and other genes are turned off in the sperm
- a setting that continues throughout
development. Therefore, the expression of
these genes depends on whether they were
inherited from the male or female parent.
¾ Normally,
this chemical reprogramming
takes months for sperm cells and years for
eggs. During cloning, however, the
reprogramming of the donor DNA must
occur within a few hours.
¾ In addition, during the same period of time
significant chromatin remodeling of the
donor DNA must occur if the cloned
embryo is to survive.
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Objective 21
Objective 21
„ Therapeutic
cloning begins the same
way as reproductive cloning.
„ However, once the embryo reaches the
blastocyst stage, it is broken apart and
the undifferentiated cells (called
embryonic stem cells) are grown into
tissue that can be used to replace the
diseased or damaged tissue of the
person who provided the DNA.
„ Therapeutic
cloning is a way to
produce new healthy tissue that is
genetically identical to the diseased or
damaged tissue of a patient.
„ The purpose of therapeutic cloning is
to supply the patient with normal
healthy tissue that will not be rejected
by the patient’s immune system.
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The early stages of therapeutic cloning (top
row) are similar to the early stages of
reproductive cloning (bottom row):
The nucleus from a skin cell of a diabetic
patient is removed.
Cell cleavage
The skin cell
nucleus is inserted occurs as the
into the enucleated embryo begins to
human egg cell. develop in vitro.
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However, in therapeutic cloning stem cells are
extracted from the embryo and grown into new
tissue for the patient who supplied the DNA:
Therapeutic Cloning
Embryonic stem cells
(ES cells) are extracted
and grown in culture.
The embryo
reaches the
blastocyst stage
The stem cells are developed
into healthy pancreatic islet cells
needed by the patient.
Inner cell
mass
The healthy tissue is
injected or transplanted
into the diabetic patient.
Diabetic
patient
Diabetic
patient
Healthy pancreatic islet cells
The nucleus from a skin cell of a healthy
patient is removed.
ES
Early embryo cells
Reproductive Cloning
Blastocyst
The blastocyst is kept intact and
is implanted into the uterus of a
surrogate mother.
The resulting baby is
a clone of the
healthy patient.
Healthy
patient
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Objective # 22
Objective 22
„ What
are embryonic stem cells?
„ Once an egg is fertilized, it grows into
an embryo composed of a small ball of
a few dozen identical cells. These
undifferentiated cells can develop into
any type of cell found in the adult. We
call these early cells embryonic stem
cells.
Discuss the techniques, potential
benefits, and controversy
surrounding stem cell research.
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Objective 22
embryonic stem cells can
develop into any type of tissue,
transplanted stem cells may allow
scientists to replace lost or damaged
tissue, offering cures for many
disorders that cannot now be treated.
„ However, there are serious ethical
issues because many people believe
that human life begins at conception.
Objective 22
„ Because
„ To
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avoid this objection, some people
advocate the use tissue-specific stem cells
which are present in adults. These cells
have committed to develop into a
particular tissue, but retain their ability to
grow and divide.
„ However, because these cells have reached
a more advanced stage of development
they may not be as versatile.
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