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Cellular Mechanisms
of Development
Chapter 19
Overview of Development
Development is the successive process of
systematic gene-directed 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
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Cell Division
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Cell Division
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Cell Division
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Cell Division
Caenorhabditis elegans
-One of the best developmental models
-Adult worm consists of 959 somatic cells
-Transparent, so cell division can be
followed
-Researchers have mapped out the lineage
of all cells derived from the fertilized egg
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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 11
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 cyclin-dependent 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 16
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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
-Become asymmetrically localized
following fertilization
-Cells that inherit them form muscles
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Cell Differentiation
Cytoplasmic determinants
-Female parent provides
egg with macho-1 mRNA
-Encodes a transcription
factor that can activate
expression of musclespecific 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 animal-pole cells form the mesoderm
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Cell Differentiation
Another example of induction is the formation
of notochord and mesenchyme in tunicates
-Arise from mesodermal cells that form at
the vegetal margin of 32-cell stage embryo
-Cells receive a chemical signal from
underlying endodermal cells
-Anterior cells differentiate into notochord
-Posterior cells differentiate into
mesenchyme
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Cell Differentiation
The chemical signal is a fibroblast growth
factor (FGF) molecule
-The FGF receptor is a tyrosine kinase that
activates a MAP kinase cascade
-Produces a transcription factor that
triggers differentiation
Thus, the combination of macho-1 and FGF
signaling leads to four different cell types
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Cell Differentiation
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Cell Differentiation
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Cell Differentiation
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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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Cloning
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
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Cloning
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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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Cloning
Early reports on a variety of adult stem cells
indicated that they may be pluripotent
-Since then these
results have been
challenged
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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
Before fertilization, specialized nurse cells
move maternal mRNAs into maturing oocyte
-These mRNA will initiate a cascade of gene
activations following fertilization
Embryonic nuclei do not begin to function until
approximately 10 nuclear divisions later
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Drosophila Embryogenesis
After fertilization, 12 rounds of nuclear division
without cytokinesis produces a syncytial
blastoderm
-4000 nuclei in a single cytoplasm
Membranes grow between the nuclei forming
the cellular blastoderm
Within a day of fertilization, a segmented,
tubular body is formed
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Drosophila Embryogenesis
Nüsslein-Volhard and Wieschaus elucidated
how the segmentation pattern is formed
-Earned the 1995 Nobel Prize
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
specify different cell fates along an axis
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Establishment of the A/P axis
Nurse cells secrete maternally produced bicoid
and nanos mRNAs into the oocyte
-Differentially 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 A/P axis
Bicoid and Nanos control translation of two
other maternal mRNAs, hunchback and
caudal, that encode transcription factors
-Hunchback activates anterior structures
-Caudal activates posterior structures
The two mRNAs are not evenly distributed
-Bicoid inhibits caudal mRNA translation
-Nanos inhibits hunchback mRNA translation
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Establishment of the D/V axis
Maternally produced dorsal mRNA is placed
into the oocyte
-Not asymmetrically localized
Oocyte nucleus synthesizes gurken mRNA
-Accumulates in a crescent on the future
dorsal side of embryo
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
-All 9 genes encode transcription factors
that activate the next gene class
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Production of Body Plan
2. Pair-rule genes
-Divide the embryo into seven zones
-The 8 or more genes encode
transcription factors that regulate each
other, and activate the next gene class
3. Segment polarity genes
-Finish defining the embryonic
segments
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Production of Body Plan
Segment identity arises from the action of
homeotic genes
-Mutations in them lead to the appearance
of normal body parts in unusual places
-Ultrabithorax
mutants produce
an extra pair of
wings
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Production of Body Plan
Homeotic gene complexes
-The HOM complex genes of Drosophila
are grouped into two clusters
-Antennapedia complex, which governs
the anterior end of the fly
-Bithorax complex, which governs the
posterior end of the fly
-Interestingly, the order of genes mirrors the
order of the body parts they control
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Production of Body Plan
Homeotic gene complexes
-All of these genes contain a conserved
180-base sequence, the homeobox
-Encodes a 60-amino acid DNA-binding
domain, the homeodomain
-Homeobox-containing genes are termed
Hox genes
-Vertebrates have 4 Hox gene clusters
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Production of Body Plan
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Production of Body Plan
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Pattern Formation in Plants
The predominant homeotic gene family in
plants is the MADS-box genes
-Found in most eukaryotic organisms,
although in much higher numbers in plants
MADS-box genes encode transcriptional
regulators, which control various processes:
-Transition from vegetative to reproductive
growth, root development and floral organ
identity
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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
equal-sized daughter cells will result
-If spindle is off to one side, two
unequal daughter cells will result
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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
all animals
-“Death program” pathway consists of:
-Activator, inhibitor and apoptotic
protease
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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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Development of Seed Plants
Plant development occurs in five main stages:
1. Early embryonic cell division
-First division is off-center
-Smaller cell divides to form the embryo
-Larger cell divides to form suspensor
-Cells near it ultimately form the root
-Cells on the other end, form the shoot
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Development of Seed Plants
2. Embryonic tissue formation
-Three basic tissues differentiate:
-Epidermal, ground and vascular
3. Seed formation
-1-2 cotyledons form
-Development is arrested
4. Seed germination
-Development resumes
-Roots extend down, and shoots up
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Development of Seed Plants
5. Meristematic development and
morphogenesis
-Apical meristems at the root and shoot
tips generate a large numbers of cells
-Form leaves, flowers and all other
components of the mature plant
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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 bloodborne agents in the mother
-Thalidomide, a sedative drug
-Many pregnant women who took it
had children with limb defects
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Environmental Effects
Endocrine disrupting chemicals (EDCs)
-Interfere with synthesis, transport or
receptor-binding of endogenous hormones
-Derived from three main sources
-Industrial wastes (polychlorinated
biphenyls or PCBs)
-Agricultural practices (DDT)
-Effluent of sewage-treatment plants
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