Transcript Document

Cellular Mechanisms
of Development
Chapter 19
Overview of Development
Development is the successive process of systematic genedirected changes throughout an organism’s life cycle.
-Can be divided into four subprocesses:
-Growth (cell division)
-Differentiation
-Pattern formation
-Morphogenesis
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Cell Division
After fertilization, the diploid zygote undergoes a period of
rapid mitotic divisions:
-In animals, this period is called cleavage;
-Controlled by cyclins and cyclindependent
kinases (Cdks).
During cleavage, the zygote is divided into smaller & smaller
cells called blastomeres:
-Moreover, the G1 and G2 phases are shortened or
eliminated.
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Cell Division
C. elegans- nematode with 959 somatic cells
Because of the absence of the two gap/growth phases, the rapid rate of
mitotic divisions during cleavage is never again approached in the lifetime
of an animal.
Example: zebrafish blastomeres divide once every several minutes during
cleavage to create an embryo with a thousand of cells in just under 3
hours!!!
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Cell Division
Blastomeres are nondifferentiated and can give rise to any
tissue.
Stem cells are set aside and will continue to divide while
remaining undifferentiated:
-Tissue-specific: can give rise to only one tissue;
-Pluripotent: can give rise to multiple different cell types;
-Totipotent: can give rise to any cell type.
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Cell Division
Cleave in mammals continues for 5-6 days
producing a ball of cells, the blastocyst.
-Consists of:
-Outer layer = Forms the placenta
-Inner cell mass = Forms the embryo
-Source of embryonic stem cells
(ES cells)
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Cell Division
A plant develops by building its body outward:
-Creates new parts from stem cells contained in structures
called meristems;
-Meristematic stem cells continually divide
-Produce cells that can differentiate into the various
plant tissues: leaves, roots, branches, and flowers
The plant cell cycle is also regulated by cyclins and cyclindependent kinases.
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Cell Differentiation
A human body contains more than 210 major types of
differentiated cells.
Cell determination commits a cell to a particular
developmental pathway:
- Can only be “seen” by experiment;
- Cells are moved to a different location in
the
embryo;
- If they develop according to their new
position,
they are not determined.
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Normal
Not Determined
(early development)
No donor
Donor
Tail cells are
transplanted
to head
Recipient
Before Overt
Differentiation
Determined
(later development)
Tail
Tail cells are
transplanted
to head
Head
Recipient
After Overt
Differentiation
Tail cells develop
into head cells in head
Tail cells develop
into tail cells in head
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Cell Differentiation
Cells initiate developmental changes by using transcriptional
factors to change patterns of gene expression.
Cells become committed to follow a particular developmental
pathway in one of two ways:
1) via differential inheritance of cytoplasmic determinants;
2) via cell-cell interactions.
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Cell Differentiation
Cytoplasmic determinants
- Tunicates are marine invertebrates;
- Tadpoles have tails, which are lost
during metamorphosis into the adult;
- Egg contains yellow pigment
granules that become asymmetrically
localized following fertilization:
-Cells that inherit them form
muscles
- Female parent provides egg with
macho-1 mRNA
-Encodes a transcription factor
that can activate expression of
muscle- specific genes
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Cell Differentiation
Induction is the change in the fate of a cell due to interaction
with an adjacent cell.
If cells of a frog embryo are separated:
-One pole (“animal pole”) forms ectoderm
-Other pole (“vegetal pole”) forms endoderm
-No mesoderm is formed
If the two pole cells are placed side-by-side, some animalpole cells form the mesoderm.
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Cloning
Until very recently, biologists thought that determination
and cell differentiation were irreversible in animals.
Nuclear transplant experiments in mammals were
attempted without success.
Finally, in 1996 a breakthrough!
Geneticists at the Roslin Institute in Scotland performed the
following procedure:
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Continuing…
1. Differentiated mammary cells were removed from the udder
of a six-year old sheep;
2. Eggs obtained from a ewe were enucleated;
3. Cells were synchronized to a resting state;
4. The mammary and egg cells were combined by somatic cell
nuclear transfer (SCNT);
5. Successful embryos (29/277) were placed in surrogate
mother sheep;
6. On July 5, 1996, Dolly was born.
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Cloning
Dolly proved that determination in animals is reversible:
-Nucleus of a differentiated cell can be reprogrammed
to be totipotent.
Reproductive cloning refers to the use of SCNT to
create an animal that is genetically identical to another.
-Scientists have cloned cats, rabbits, rats, mice, goats
and pigs.
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Cloning
Reproductive cloning has inherent problems:
1. Low success rate
2. Age-associated diseases
Normal mammalian development requires precise genomic
imprinting:
-The differential expression of genes based on parental
origin.
Cloning fails because there is not enough time to reprogram
the genome properly.
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Cloning
In therapeutic cloning, stem cells are cloned from a person’s
own tissues and so the body readily accepts them.
Initial stages are the same as those of reproductive cloning:
-Embryo is broken apart and its embryonic stem cells
extracted;
-Grown in culture and then used to replace diseased or
injured tissue.
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Cloning
Human embryonic stem cells have enormous promise for
treating a wide range of diseases;
-However, stem cell research has raised profound ethical
issues.
Very few countries have permissive policy towards human
reproductive cloning;
-However, many permit embryonic stem cell research.
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Pattern Formation
In the early stages of pattern formation, two perpendicular
axes are established:
-Anterior/posterior (A/P, head-to-tail) axis;
-Dorsal/ventral (D/V, back-to-front) axis.
Polarity refers to the acquisition of axial differences in
developing structures.
Position information leads to changes in gene activity, and
thus cells adopt a fate appropriate for their location.
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Drosophila Embryogenesis
Drosophila produces two body forms:
-Larva – Tubular eating machine
-Adult – Flying sex machine axes are established
Metamorphosis is the passage from one body form to
another.
Embryogenesis is the formation of a larva from a fertilized
egg.
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Drosophila Embryogenesis
Two different genetic pathways control the establishment of
the A/P and D/V polarity:
-Both involve gradients of morphogens
-Soluble signal molecules that can
different cell fates along an axis.
specify
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Continuing…
Nurse cells secrete maternally
produced bicoid and nanos
mRNAs into the oocyte that will be
transported by microtubules to
opposite poles of the oocyte:
-bicoid mRNA to the future
anterior pole;
-nanos mRNA to the future
posterior pole.
After fertilization, translation will
create opposing gradients of
Bicoid and Nanos proteins.
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Establishment of the D/V axis
Maternally produced dorsal mRNA is placed into the
oocyte.
-Not asymmetrically localized.
After fertilization, a series of steps results in selected
transport of Dorsal into ventral nuclei, thus forming
a D/V gradient
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Production of Body Plan
The body plan is produced by sequential activation of three
classes of segmentation genes:
1. Gap genes
-Map out the coarsest subdivision along the A/P axis.
2. Pair-rule genes
-Divide the embryo into seven zones (Fig 19.13).
3. Segment polarity genes
-Finish defining the embryonic segments.
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Morphogenesis
Morphogenesis is the formation of ordered form and
structure:
-Animals achieve it through changes in:
-Cell division
-Cell shape and size
-Cell death
-Cell migration
-Plants use these except for cell migration.
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Morphogenesis
Cell division
-The orientation of the mitotic spindle determines the
plane of cell division in eukaryotic cells:
-If spindle is centrally located, two
daughter cells will result;
-If spindle is off to one side, two
cells will result.
equal-sized
unequal daughter
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Morphogenesis
Cell shape and size
-In animals, cell differentiation is accomplished by
profound changes in cell size and shape:
-Nerve cells develop long processes
called axons;
-Skeletal muscles cells are large and
multinucleated.
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Morphogenesis
Cell death
-Necrosis is accidental cell death;
-Apoptosis is programmed cell death:
-Is required for normal development in
-“Death program” pathway consists of:
-Activator, inhibitor and apoptotic
protease
all animals
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Morphogenesis
Cell migration
-Cell movement involves both adhesion and loss of
adhesion between cells and substrate;
-Cell-to-cell interactions are often mediated through
cadherins;
-Cell-to-substrate interactions often involve complexes
between integrins and the extracellular matrix
(ECM).
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Environmental Effects
Both plant and animal development are affected by
environmental factors:
-Germination of a dormant seed proceeds only under
favorable soil and day conditions;
-Reptiles have a temperature-dependent sex
determination (TSD) mechanism;
-The water flea Daphnia changes its shape after
encountering a predatory fly larva.
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Environmental Effects
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Environmental Effects
In mammals, embryonic and fetal development have a
longer time course .
Thus they are more subject to the effects of environmental
contaminants, and blood-borne agents in the mother:
-Thalidomide, a sedative drug. Many pregnant
women who took it had children with limb defects.
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