View larger version (26K):
[in this window]
[in a new window]
|
Fig. 2. Examples of regulatory feedback involved in positional specification by
morphogen gradients. (A) The gap gene system of Drosophila
melanogaster. Maternal morphogen gradients (such as Bcd) bias target
nuclei towards the expression of specific gap genes according to their
position along the anteroposterior (AP) axis of the embryo. The positions of
the central and posterior domains of Krüppel (Kr),
knirps (kni), giant (gt) and
hunchback (hb) are shown diagrammatically, indicating the
two pairs of staggered, mutually complementary domains along the AP axis
(anterior, left). Cross-repressive feedback between complementary gap genes
stabilises and sharpens these patterns (thick T-bars). A second layer of
cross-repression with posterior dominance (thin T-bars) leads to anterior
shifts in expression domain boundaries (indicated by coloured arrows).
(B) Feedback between signalling ligands (morphogens) and their
receptors or downstream pathways in the Drosophila wing disc. (Left)
Hedgehog (Hh) signalling upregulates Patched (Ptc) receptor expression, which
inhibits Hh movement by sequestering it extracellularly. (Centre) Wingless
(Wg) signalling downregulates expression of its receptor Frizzled2 (Fz2) close
to the Wg source. High levels of Fz2 away from the source stabilise the Wg
protein. (Right) Decapentaplegic (Dpp) signalling downregulates expression of
its receptor Thickveins (Tkv) close to its source. Tkv in turn sensitises
cells away from the source to low levels of Dpp signalling. (C) Sonic
Hedgehog (Shh) in the vertebrate neural tube (NT) is regulated by multiple
levels of feedback. Shh (blue circles) up-regulates expression of its receptor
Ptc1 (red), which inhibits signalling by repressing the co-receptor Smoothened
(Smo, orange circles). This desensitises cells in the region of the gradient
where ligand is limiting (in the dorsal NT, right) and alters the shape of the
gradient (indicated by different blue shading). Yellow stars indicate
signalling events. Brief Shh signalling activity induces expression of the
target gene Olig2 (white). Maintained levels of Shh induce
Nkx2.2 (blue), which in turn represses Olig2 (T-bar). Red
indicates dorsal (Class I) Shh target genes, such as Irx3 and Pax6. (D)
Dorsoventral patterning in the Drosophila embryo. Dpp/Scw
heterodimers diffuse dorsally in a complex with Twisted Gastrulation (Tsg) and
Short Gastrulation (Sog). They are captured and enriched at the dorsal midline
by a surface bound ligand binding protein (SBP), whose expression is
upregulated by Dpp signalling. This leads to the sharpening and narrowing of
the dorsal stripe of Dpp activity (measured as the concentration of
phosphorylated MAD, pMAD) through bistability in the cellular response.
|
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
). Positional
specification by a morphogen gradient is implemented as a two-step process.
Step 1: localised production of a morphogen at its source (green cell) and
degradation at its sink (pink cell) leads to a linear gradient of decreasing
morphogen concentration through the as yet undifferentiated tissue. Cells in
the tissue sense whether they are exposed to morphogen concentrations below or
above given thresholds (T1, T2). Step 2: cells become
specified and later differentiate by turning on specific target genes
(indicated by blue, white and red). Boundaries of target gene expression
correspond exactly to the thresholds in the gradient. The arrow indicates the
strictly feed-forward flow of information in this system. This `classical'
two-step view of positional specification naturally extends to more realistic
non-linear gradients and systems where degradation is not restricted to a
sub-population of cells (Slack,
1987