Environmental Regulation of Development

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Environmental Regulation of Development
Many reptiles have their sex determined by the
temperature at 30 oC, mostly females are
produced at 34 oC, mostly males are produced
very important for wildlife management and
breeding could temperature change have killed
off the dinosaurs?
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Environmental Regulation of Development
other phenotypes can also be determined by the
environment temperature and day length regulate
the development of butterflies summer dark
color spring light color originally
characterized as different species-- colors are
very different morph phenotypic variation
caused by the environment
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Environmental Regulation of Development
some moths also have different coloration
spring caterpillars eat oak catkins-
ressemble them summer caterpillars have not
more oak catskins to eat-- look like
twigs difference in diet regulate the
appearance pink flamingos are pink due to the
shrimp they eat sheep grow longer hair in the
winter reaction norm range of phenotypes found
over the spectrum of conditions
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Environmental Regulation of Development
one thing many organisms have to deal with is UV
light UV light causes mutations via thimine
dimers eggs use natural sunscreens, particularly
marine organisms sunlight induces the
expression of pigments that absorb UV
radiation mutations in these pigments can cause
developmental abnormalities teratogens
environmental condition/chemicals that cause
developmental defects
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Environmental Regulation of Development
many amphibian/reptile species currently in
decline are least able to repair thymine
dimers enzyme levels varied by nearly 2 orders
of magnitude most enzyme present in embryos
that developed in the sun amphibians with less
repair enzyme have more deformed embryos when
exposed to UV light than those with more repair
enzyme
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Environments Vary within an Embryo
just like outside environments can regulate
development, embryonic environment can also
change cell fates-- interactions between cells
and their neighbors will change what they
become differentiation development of
specialized cell types as in dictyostelium commit
ment cell doesn't differ phenotypically yet, but
the decision to become something else has
already been made specification initial phase
of commitment where a cell has made a choice
that will be caried unless something reverses its
decision determination second phase of
commitment where a decision is not able to be
reversed when it previously could be
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Autonomous Specification
3 different modes of cells committing and
differentiating autonomous specification makes
the same types of cell in a dish as it would
in an embryo-- other cells in the embryo can't
make the cells mosaic development indpendent
groups of cells become different parts C elegans
is the best studied example-- entire cell
history of every cell in the embryo is known
and traced cells have a limited choice of
cell types at any given point
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Autonomous Specification
morphogenic determinants something in the cell
which determines type ie. polar granules in C
elegans determine germ cells of the embryo in
tunicates, cells can be taken out of the embryo
and will form the same type of cell as they
normally would
EMS
P2
ABa
ABp
presumptive trochoblasts remember what they
should become, even in isolation
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Conditional Specification
conditional specification a cell becomes one of
several options based on interactions between
various other cells under this model of
differentiation, cells that remain can take over
the fates of cells that are removed regulative
development ability of cells to become any or
all cell types can often take on fates that
they normally would not in the animal
typically the case in vertebrate
development identical twins form from a split
single embryo, each of which forms a complete
organism
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Conditional Specification
conditional specification came out of ideas
suggesting autonomous fates germ plasm theory
idea that sperm and egg provide equal
contributions both qualitatively and
quantitatively, to the embryo initially,
different chromosomes were believed to go to
different cells makes sense in many ways--
cells are clearly different from each other
germ cells would be special in that they contain
all the chromosomes this suggests cells would
have a restricted set of properties-- ie.
autonomous development and suggested a series of
experiments defect experiment destroying a
portion of an embryo, then watch isolation
experiment remove part of the embryo, watch
removed part recombination experiment replace
part of the embryo with a new part transplantation
experiment remove one part and replace with the
same part from a different embryo-- first used
in fate maps
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Conditional Specification
killing one cell of a 2 cell stage tadpole (and
leaving the debris there) causes a half an
embryo to form-- what you might expect from
autonomous development--left or right half of a
tadpole- defect xpt actually separating
blastomeres of a 4 cell sea urchin embryo causes
4 normal embryos to form-- isolation
experiment first evidence that cells in some
organisms could become cells that they
normally would not
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Conditional Specification
so why did the frog defect experiment form only
half an embryo? repeating isolation experiments
with frog blastomeres behaved the same way as
the sea urchin cells-- general feature of
vertebrate development something specific in the
killed cell that was left told the rest of the
embryo it was there- cells talk to each other
and can differentiate
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Morphogenic Gradients
morphogen soluble instructive molecule secreted
at a distance from the target when a
substance is secreted, it diffuses so that there
is a high local concentration and decreasing
concentrations at greater distances cells in
different parts of this concentration gradient
can receive different signals and become
different cell types Ephrins are signaling
molecules that regulate the formation of
connections in the brain
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Morphogenic Gradients
same holds true for extracellular gradients as
shown in flatworms cutting off the heads or the
tails of flatworms both halves regenerate
the missing half, not the same half leave most
of the middle, both front and back
regenerate with only a small part of the middle
the regeneration fails
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Morphogenic Gradients
for a substance to be considered a morphogen,
cells must respond directly to that substance
based on its concentration activin a protein
from frogs that affects different cells based on
activin increases gene expression related to
the formation of mesoderm has several related
TGF-b signaling molecules like nodal (below)
mouse nodal in situ
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Morphogenic Gradients
concentration of activin causes blastomeres to
adopt different fates
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Morphogenic Gradients
morphogenetic field group of cells where
position within certain boundaries determines
the cell fate ie. imaginal disks in flies stay
imaginal disks no matter where they are
transplanted in an embryo-- they can become leg
or wing or antenna,etc but individual cells
are not committed to a particular cell
type cells within a morphogenetic field interact
among themselves to determine what type of
cell within a field they will become
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Stem Cells
stem cell cell that is able to become a variety
of different specialized cells and can divide
indefinitely embryonic stem cell cell that can
become any type of cell in an embryo
originally isolated from blastula stage embryos
pluripotent ability to differentiate into any
of the cells of the embryo totipotent ability
to differentiate into cells of the embryo and
fetal placenta (tropoblast) committed stem
cell stem cells that can give rise to an
incomplete subset of specialized cells
numerous different committed stem cells exist,
neural, hematopoeitic... progenitor cell (aka
precursor cell) divides and forms specialized
cells have lost the ability to replicate
repeatedly-- limited of divisions once
formed, they always make the same kind of cells
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Stem Cells
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Stem Cells
embryonic stem cells grow as colonies, usually on
glial cells with leukemia inhibiting factor
(LIF) in the media
ES cells want to differentiate-- they express
certain markers while stem cells, but if balls
of cells grow too large, some markers change
and are thus NOT ES cells anymore but are some
committed cell type
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Syncytial Specification
syncitial specification interactions within a
single cell are used to tell cells what they
will become generally occurs in
insects syncitial blastoderm collection of many
nuclei within a single large egg that are not
separated by cell membranes
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Syncytial Specification
Within the fly egg, two proteins, bicoid and
nanos form inverse gradients
these gradients (established by the mother)
induce other genes based on their concentration
(similar to a morphogenic gradient) called gap
genes gap genes regulate pair rule genes, which
regulate segment polarity genes, which
regulate... at different stages of development,
flies (and other organisms) also use a
combination of autonomous and regulated
development to form the entire embryo
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5 Major Questions of Morphology
1) How are tissues formed from populations of
cells? tissues have a specific organization of
cells that arrange themselves 2) How are organs
constructed from tissue? tissues form
separately but function together- how do they
relate 3) How do organs know where to form and
cells know where to migrate? cells need to
know where they are supposed to be and only form
there 4) How is organ growth coordinated during
development? more cells divide in the
intestine/skin than in the brain-- how is it
done 5) How do organs achieve polarity? cells
are oriented and arranged differently in
different parts of the body
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Cell and Tissue Morphology
2 major types of cell arrangements in the
embryo 1) epithelial cells-- tightly connected
sheets or tubes of cells 2) mesenchymal cells--
independent, unconnected cells
epithelial cells mesenchymal cells
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Cell and Tissue Morphology
within these 2 types of arrangements there are
several ways cells organize a)
direction/orientation of cell divisions b) cell
shape changes c) cell movement/migration d)
cell growth e) cell death-- not every cell born
lives f) change membrane or secreted products
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Differential Cell Affinity
Cells interact with each other almost exclusively
at the cell surface proteins on the cell
surface recognize other cells, receive signals
such as morphogens, and send out their own
signals selective affinity preferences of
particular cell types/ germ layers to stick to
like cells rather than unlike
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Differential Cell Affinity
additionally, early aggregates assume the same
positions in vitro as they would in the
embryo-- epithelial cells on the outside,
endoderm inside, mesoderm in
between histotypic aggregation organization of
complex tissue from single cells
Selective affinity changes during development-
cells move and change over time- later cells do
not behave the same as early ones
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Differential Cell Affinity
differential adhesion hypothesis cells stick
together in order to make the most stable
overall structure (ie. cells alway move toward
lower energy) strongest interactions would most
compact the next strongest, then the next,
etc. like cells that stick together better
than they stick to other cell types will
effectively group together because they stick
when they encounter others pigment epithelium
12.6 dynes/cm neural retina 1.6 dynes/cm sort
very clearly, as in figure
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Cell Adhesion Molecules
Cadherins large family of calcium dependent
adhesion molecules bind homophilically to each
other-- N with N, E with E, etc transmembrane
proteins that all bind to the same intracellular
proteins catenins complex of 3 proteins which
anchor the cadherins to actin at least one of
these proteins (b catenin) can also act as a
signal a catenin binds directly to actin
cytoskeleton E cadherin initially on all
embryo cells, becomes restricted to epithelial P
cadherin primarily on tropoblasts (placenta) and
uterine wall N cadherin initially on mesodermal
cells, primarily expressed on neurons C
cadherin expressed on blastomere cells and
critical for gastrulation
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Cell Adhesion Molecules
homophilic binding occurs at the N terminus-- C
terminus is in the cytoplasm calcium ions hold
the domains as a rigid rod-- required for
good adhesion mediates a lot of early adhesion
during development expressing more P cadherin on
the surface makes stronger interactions and
causes those cells to be on the inside of a
group of cells
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Cell Adhesion Molecules
tropoblasts early cells of embryos that will
form part of the placenta express both P and E
cadherins P cadherins allow the embryo to bind
to the uterine wall in mammals-- required for
the embryo to survive E cadherins allow the
tropoblasts to bind to the rest of the embryo,
anchoring the cells to the uterus
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Cell Adhesion Molecules
other families of adhesion molecules play vital
roles in development integrins a/b dimers that
recognize distinct amino acid sequences on
exposed regions of cell surface proteins-- RGD is
the most common link to specific kinases in
the cytoplasm kinase protein that
phosphorylates other (usually specific)
proteins immunoglobulin (Ig) superfamily
largest class of adhesion molecules bind both
homophilically (like molecules) and
heterophilically (unlike) contains multiple (1
to 20) repeats of the protein domain in
antibodies links to a variety of cytoplasmic
proteins, including kinases and actin vital
roles best understood in the immune and nervous
systems lectins class of proteins that bind to
specific carbohydrate (sugars) groups bind
various glycoproteins (ie. gp80 in
dictyostelium) are vital for immune cell
function and recognition, also found elsewhere