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Fig. 7. Model for the regulation of morphogen signaling by LDA. (A) In the absence
of LDA, the morphogen (pink circle) produced from a restricted area of the
tissue will travel over a field of cells. When the morphogen molecules run
into a cell that expresses a signal-transducing receptor (blue cell surface
molecule), some of them will bind to the receptor to induce signal
transduction (blue arrows), while the rest will move on to the next cell to
form a concentration gradient. (B) In the presence of LDA, the antagonists
(red cell surface molecule) will compete with the signal-transducing receptors
for a limited amount of ligand, and thus decrease the pathway activity within
a cell (one blue arrow instead of two in A) at a given concentration of
morphogen (cell-autonomous effect). In addition, as the ligands will bind to
both receptors and antagonists, less of them will move on to the next cell,
which will affect morphogen distribution in the tissue (non-cell autonomous
effect). (C) Cell-autonomous and non-cell autonomous effects of LDA together
will decrease the magnitude and range of the morphogen signaling gradient. (D)
The neural tube patterning defects of
MtPtch1;Ptch1-/-;Hhip1-/- embryos are in
agreement with the model in A-C (see text).
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