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Fig. 7. Two-step model for R8 specification. (A) Our model for lateral inhibition
during R8 specification proposes both activation of N in cells inhibited from
R8 fate and inactivation of N in cells taking R8 fate. Notch signaling is
indicated by shading. Darker shading corresponds to more intense Notch
activity. The model proposes two routes for adopting non-R8 fate. In some
cells, N activation by Dl is sufficient to block R8 specification. In other
cells, less N activation occurs, leading to an intermediate state in which R8
specification is possible if N becomes insensitive to activation by Dl, and
inhibition of R8 fate is possible if further activation of N by Dl occurs. The
mechanism of desensitization is not known but might involve EGF repeat 14 of
the N extracellular domain (Li et al.,
2003 ). Sca and Gp150 promote sensitivity to Dl in such cells (or
antagonize the block to Dl), allowing some cells in this intermediate state to
activate N and avoid R8 specification. (B) R8 cells retain sensitivity to Dl
in the spl mutant allele of N (Li
et al., 2003). Such activity depends on Sca and Gp150, and is
interpreted here as a shift in the equilibrium away from R8 specification back
towards the intermediate state. Persistent N signaling in differentiating R8
cells is the cause of abnormalities in spl mutants
(Li et al., 2003). (C) In the
absence of Dl, no lateral inhibition occur and all cells competent to do so
take R8 fate. (D) In the absence of Sca or Gp150, cells in the intermediate
state tend to lose Dl sensitivity and take R8 fate. Two distributions of cells
seem most at risk of acquiring R8 fate this way. One is cells closest to the
actual R8 precursor and which have the highest probability of replacing it.
The other would be cells distant from neural precursors, where the influence
of Dl might be weakest and the level of N signaling lowest. In fact these are
the locations where ectopic neural cells arise in sca or
gp150 mutants. Supernumerary R8 and bristle precursors propose both
adjacent to normal precursors and at a distance from them
(Baker and Zitron, 1995). We
propose that these cells have greatest need of Sca and Gp150 to promote N
activity and prevent protection from Dl.
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41-514 shows concentration in N-expressing cells, although reduced
compared with that of full-length Sca (compare with D). (H) Sixty minutes
after heatshock-induced expression, Sca