PowerPoint Presentation Smith Gurdon 2001

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The French Flag problem and a solution
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Development of the chick wing
Humerus (not shown!)
10 days
3 days
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Graft of a ZPA induces a mirror-image duplication
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Pattern of digits depends on the position of the
graft
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Digit pattern depends on the strength of the
polarising region
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Different numbers of cell specify different digits
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A normal limb stays at about the same width
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A duplicated limb gets wider
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If you prevent widening in a duplicated limb, it
is as if the concentration of morphogen in the
centre of the wing cannot get low enough
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Sonic hedgehog is expressed in the ZPA
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Expression of Shh is correlated with ZPA activity
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Sonic hedgehog induces additional digits in the
chick limb in a concentration-dependent fashion
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these data lead us to propose a new model for
digit patterning. We suggest that Shh initially
acts long range to prime the region of the limb
competent to form digits and thus control digit
number. Then later, Shh acts short range to
induce expression of Bmps, whose morphogenetic
action specifies digit identity.
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A Xenopus tadpole
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Mesoderm induction
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Experiment to study concentration-dependent
effects of activin
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Response of Xbra to different concentrations of
activin Xbra behaves like the white stripe in
the French Flag
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Regulation of Xenopus Brachyury by an activin
gradient?
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Different concentrations of activin are required
for optimal activation of Xbra and goosecoid
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Activin can create a French Flag
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Long-range signalling by derrière
Inducer
RNA
FLDx
Fuse and culture fo
r 3 hours
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A gradient of activin can specify domains of
expression of Xbra and goosecoid
Xbra
Xbra
Goosecoid
Goosecoid
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Labelled activin diffuses from a bead and sets up
a gradient
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Its activin (or an activin-like molecule) which
is active at a distance there is no evidence for
a relay
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TGFb can act over a long range too
Weak beads
Strong beads
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No polarity in the responding cells they can
signal in either direction
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Constitutively active activin receptors do not
establish a relay
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Only a small proportion of receptors need be
occupied for differential gene activation. Xbra
induction requires about 100 molecules per cell,
goosecoid about 300.
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An activated form of the ALK-4 type I activin
receptor can elicit threshold responses
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Gradual refinement of activin thresholds (2)
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Threshold formation requires protein synthesis in
the responding cells
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Expression of dpp and its targets omb and spalt
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Over-expression of dpp (E,G) or activation of dpp
receptors (F,H) expands omb and spalt expression
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Activated dpp receptor causes cell-autonomous
induction of omb
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Activated dpp receptor causes cell-autonomous
induction of spalt
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Dpp acts at long range to activate omb
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Dpp acts at long range to activate spalt
Local activation of dpp makes a bulls-eye
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Wing disk cells require dpp receptor function to
respond to dpp
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omb and spalt are induced by different
concentrations of DPP
Normal expression
Weaker dpp activation induces smaller domain of
omb
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Weaker dpp activation does not induce spalt
Up-regulation of dpp in its normal expression
domain causes expansion of spalt
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