Introduction To Pattern Formation

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Introduction To Pattern Formation

• Autonomous Conditional Cell Specification,
  Fields Morphogens

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Cellular Differentiation

• All Cells have the same genes
• Some genes are expressed in all cells
• Housekeeping genes
• Some genes are expressed only in specific cells
• Luxury genes
• Zygotes are totipotent
• Can form any cell in the organism
• Embryonic cells are pluripotent
• Differentiated cells are restricted in potential

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Fate Maps
Prospective Significance Prospective
Potency
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Autonomous (Mosaic) Specification in a Tunicate
Embryo
Figure 3.8. Autonomous specification in the
early tunicate embryo.When the four blastomere
pairs of the 8-cell embryo are dissociated, each
forms structures that it would have formed if it
had remained in the embryo. (The fate map of
the tunicate shows that the left and right sides
produce identical cell lineages.) (After
Reverberi and Minganti 1946.)

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Conditional Specification-Regulative Development
in a Frog
Figure 3.11. Conditional specification. (A) What a cell becomes depends upon its position in the embryo. Its fate is determined by interactions with neighboring cells. (B) If cells are removed from the embryo,the remaining cells can regulate and compensate for the missing part.

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Autonomous vs. Conditional Specification
I. Autonomous specification (Prospective potencyProspective significance)
Characteristic of most invertebrates.
Specification by differential acquisition of certain cytoplasmic molecules present in the egg.
Invariant cleavages produce the same lineages in each embryo of the species. Blasto mere fates are generally invariant.
Cell type specification precedes any large-scale embryonic cell migration.
Produces "mosaic" ("determinative") development cells cannot change fate if a blasto mere is lost.
II. Conditional specification (PPgtPS)
Characteristic of all vertebrates and few invertebrates.
Specification by interactions between cells. Relative positions are important.
Variable cleavages produce no invariant fate assignments to cells.
Massive cell rearrangements and migrations precede or accompany specification.
Capacity for "regulative" development allows cells to acquire different functions
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Another Way of Looking At It

• Animal development can proceed according to
  either the American or the European plan. Under
  the European plan (autonomous specification), you
  are what your progenitors were. Lineage is
  important. Under the American plan (conditional
  specification), the cells start off undetermined,
  but with certain biases. There is a great deal of
  mixing, lineages are not critical, and one tends
  to becomes what one's neighbors are - Sydney
  Brenner (quoted in Wilkins 1993)

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The Limb Field
Figure 3.23. Prospective forelimb field of the
salamander Ambystoma maculatum. The central area
contains cells destined to form the limb per se
(the free limb). The cells surrounding the free
limb give rise to the peribrachial flank tissue
and the shoulder girdle. The ring of cells
outside these regions usually is not included
the limb, but can form a limb if the more
central tissues are extirpated. (After Stocum and
Fallon 1983.)
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FGF10 Expression Defines The Limb Field
Figure 16.4. FGF10 expression and action in the
developing chick limb. (A) FGF10 becomes
expressed in the lateral plate mesoderm in
precisely those positions where limbs normally
form. (B) When cells genetically constructed to
secrete FGF10 are placed into the flanks of
chick embryos, the FGF10 can cause the formation
of an ectopic limb (arrow). (From Ohuchi et al.
1997 courtesy of S. Noji.)
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Limb Bud Formation
Figure 16.3. Limb bud formation. (A)
Proliferation of mesodermal cells from the
somatic region of the lateral plate mesoderm
causes the Limb bud in the amphibian embryo to
bulge outward. These cells generate the skeletal
elements of the limb. Contributions of cells from
the myotome provide the source of the limb's
musculature. (B) Entry of myotome cells (purple)
into the limb bud. This computer reconstruction
was made from sections from an in situ
hybridization to the myf5 mRNA found in
developing muscle cells. If you can cross your
eyes, the three dimensionality of the stereogram
will become apparent. (B courtesy of J. Streicher
and G. Müller.)
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The Skeletal Elements of The Chick Wing
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Tissue Interactions

• Induction- the presence of one tissue is required
  for the formation of a structure in another.
• Instructive interaction The inducing tissue
  informs the fate of the responding tissue.
• Permissive The inducing tissue is necessary for
  the response to occur but not sufficient to
  specify ultimate cell fates (Cell fate
  information is in the responding tissue)

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Establishing the Proximal Distal Axis
AER Required for outgrowth P/D Axis AER not
responsible for Specification A/P Axis AER is
permissiveMesoderm is instructive AER
Maintained by Mesoderm AER secretes FGF

Figure 16.8. Summary of experiments demonstrating the effect of the apical ectodermal ridge (AER) on the underlying mesenchyme. (Modified from Wessells 1977.)
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The Apical Ectodermal Ridge
AER
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FGF8 Signals Limb Outgrowth
Figure 16.12. FGF8 in the AER. (A) In situ
hybridization showing expression of Fgf8 message
in the ectoderm as the limb bud begins to form.
(B) Expression of Fgf8 RNA in the apical
ectodermal ridge, the source of mitotic signals
to the underlying mesoderm. (C) In normal 3-day
chick embryos, FGF8 is expressed in the apical
ectodermal ridge of both the forelimb and
hindlimb buds. It is also expressed in several
other places in the embryo including the
pharyngeal arches. (A and B courtesy of J. C.
Izpisúa-Belmonte C courtesy of A. López-Martínez
and J. F. Fallon.)
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Evidence that led to the progress zone model
Sequential removal of the AER results in
progressively less disruption of development in a
P/D fashion.
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The Progress Zone Model For Proximal-Distal
Specification
Fig. 1. A cells proximo-distal positional value
may depend on the time it spends in the Progress
Zone. Cells continually leave the zone at the tip
of the limb under the apical ectodermal ridge.
Cells that leave early form proximal structures
while cells that leave last form the tips of the
digits. (Wolpert 2000)
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Specification by the Progress Zone
                                                
     Figure 16.11. Control of proximal-distal
specification by the cells of the progress zone.
A) Extra set of ulna and radius formed when an
early-bud progress zone was transplanted to a
late wing bud that had already formed ulna and
radius. (B) Lack of intermediate structures seen
when a late-bud progress zone was transplanted to
an early limb bud. The hinges indicate the
locations of the grafts. (From Summerbell and
Lewis 1975 photographs courtesy of D.
Summerbell.)
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An alternative model Early Allocation and
Progenitor Expansion Model (Pre-specification)

• Observations consistent with this model Cell
  division is seen throughout the limb budWhen
  AER is removed, cell death occurs about 200µm
  beneath the AER If the limb bud is a fully
  formed rudiment that grows as it develops, then
  200 µm of cell death will kill progressively
  smaller amounts of the rudiment.

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Anterior Posterior Specification

• Limb field prior to bud emergence is already
  specified for anterior/posterior, dorsal/ventral
• How is this information maintained during the
  outgrowth of the limb?
• Classical experiments
• Extensive series of experiments transplanting
  pieces of the limb bud from one region to another
  at different times in bud outgrowth.
• Only one region gave consistent pattern
  alterations

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The Zone of Polarizing Activity
Figure 16.17. When a ZPA is grafted to anterior
limb bud mesoderm, duplicated digits emerge as a
mirror image of the normal digits. (From Honig
and Summerbell 1985 photograph courtesy of D.
Summerbell.)
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The French Flag Model
Figure 3.19. The French flag analogy for the
operation of a gradient of positional
information. (A) In this model, positional
information is delivered by a gradient of a
diffusible morphogen from a source to a sink.
The thresholds indicated on the left are
cellular properties that enable the gradient to
be interpreted. For example, cells becomes blue
at one concentration of the morphogen, but as
the concentration declines below a certain
threshold, cells become white. Where the
concentration falls below another threshold,
cells become red. The result is a pattern of
three colors. (B) An important feature of this
model is that a piece of tissue transplanted
from one region of an embryo to another retains
its identity (as to its origin), but
differentiates according to its new positional
instructions. This phenomenon is indicated
schematically by reciprocal "grafts" between the
flag of the United States of America and the
French flag. (After Wolpert 1978.)
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How Could Cells A Interpret a Morphogen Gradient
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Anterior And Posterior Limb Fields Are Specified
by Position
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Questions Which Need to be Answered About
Morphogen Gradients

• What is the morphogen?
• What is the source of the morphogen?
• How do cells respond to the gradient?
• How do they sense the gradient?
• How do they change their fate in response to
  morpogen?
• What sets up the source and sink?
• What happens to the gradient over time?