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Fig. 5. Positional signals and regulatory gene expression. (A) Cell autonomous
responses of Atonal and Hairy expression to Dpp, Hh and N signal reception as
inferred from our results, illustrating the roles of Ci155 and Ci75. Positive
and negative interactions do not imply that direct molecular interactions
between proteins or between proteins and genes have been demonstrated, only
that interactions occur within the same cell without further intercellular
signals. Ci75 must repress Ato since mutation of smo imposes a delay
on differentiation that is released by deleting ci. Ci155 must
activate Ato since Mad Su(H) cells differentiate but Mad Su(H)
ci cells do not. Tkv must activate Ato independently of Ci because
ci cells differentiate normally but tkv ci and Mad
ci cells do not. Tkv is shown inhibiting Ci75, because Tkv promotes Ci155
accumulation in smo-mutant cells; this Ci155 is presumed to be
inactive. Tkv also promotes Ci155 accumulation in cells not mutant for
smo. Hairy has been shown previously to repress Ato function
(Brown et al., 1995 ). Ci155
must repress Hairy as Hairy is maintained cell autonomously by Mad Su(H)
ci-mutant cells but can be downregulated by Mad Su(H) cells. N
must repress Hairy as Hairy is maintained cell autonomously by Mad Su(H)
ci-mutant cells but can be downregulated by Mad ci cells. N may
activate Atonal independently of Hairy as well, because the furrow progresses
faster through Su(H)-mutant clones where Hairy is still expressed
(Li and Baker, 2001). Hairy
expression must be initiated in part by another signal, although Dpp has an
input, as revealed by the quantitative reduction of Hairy levels in cells
mutant for tkv (Greenwood and
Struhl, 1999) and Mad, and all their combinations with
Su(H) and ci. The network accounts for all the mutant
phenotypes. In the absence of Ci, normal differentiation occurs in response to
Dpp and N. In the absence of smo, differentiation is delayed because
activation pathways through Ci155 are lost but repression by Ci75 retained. In
the absence of both Dpp and N, differentiation occurs in response to Hh.
Absence of either tkv or N alone has little effect,
reflecting either the dominant role of Hh, or perhaps that both positive and
negative inputs are lost in each case. (B) Extracellular signaling to Atonal
and Hairy. Hh, Dl and Dpp are shown at the locations of their expression. The
signal acting most anteriorly to the morphogenetic furrow is Dpp. Dpp is
expressed at the anterior of the morphogenetic furrow in response to Hh. Dpp
promotes Hairy expression. More posteriorly, Dpp synergizes with the
relatively indiffusible Dl signal to induce Atonal. Dl is expressed in
response to Atonal, and later in response to activation of Egfr by ligands
produced by Atonal-dependent R8 cells. Hh also induces Atonal through the
Ci155/Ci75 ratio. Hh is secreted by photoreceptor cells specified by Egfr
activation by ligands produced by Atonal-dependent R8 cells. Both N and Hh
downregulate Hairy. Despite intrinsically different ranges of Dpp and Hh
signals, their activation of Ato coincides because Dpp also elevates Hairy,
which must be downregulated by Hh or Dl.
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