Ne. Baker et al., EVOLUTION OF PRONEURAL ATONAL EXPRESSION DURING DISTINCT REGULATORY PHASES IN THE DEVELOPING DROSOPHILA EYE, Current biology, 6(10), 1996, pp. 1290-1301
Background: Receptors of the Notch family affect the determination of
many cell types. In the Drosophila eye, Notch antagonises the basic he
lix-loop-helix (bHLH) protein atonal, which is required for R8 photore
ceptor determination. Similar antagonism between Notch and proneural b
HLH proteins regulates most neural cell determination, however, it is
uncertain whether the mechanisms are similar in all cases. Here, we ha
ve analyzed the sensitivity of atonal expression to Notch signalling u
sing a temperature-sensitive Notch allele, by the expression of activa
ted Notch or of the ligand Serrate, and by monitoring expression of th
e atonal-dependent gene scabrous and of the Notch-dependent Enhancer o
f split genes. Results: The atonal expression pattern evolves from gen
eral 'prepattern' expression, through transient 'intermediate groups'
to R8 precursor-specific expression. Successive phases of atonal expre
ssion differ in sensitivity to Notch. Prepattern expression of atonal
is not inhibited. Inhibition begins at the intermediate group stage, c
orresponding to the period when atonal gene function is required for i
ts own expression. At the transition to R8 cell-specific expression, N
otch is activated in all intermediate group cells except the R8 cell p
recursor. R8 cells remain sensitive to inhibition in columns 0 and 1,
but become less sensitive thereafter; non-R8 cells do not require Notc
h activity to keep atonal expression inactive. Thus, Notch signaling i
s coupled to atonal repression for only part of the atonal expression
pattern. Accordingly, the Enhancer-of-split m delta protein is express
ed reciprocally to atonal at the intermediate group and early R8 stage
s, but is expressed in other patterns before and after. Conclusions: I
n eye development, inhibition by Notch activity is restricted to speci
fic phases of proneural gene expression, beginning when prepattern dec
ays and is replaced by autoregulation. We suggest that Notch signallin
g inhibits atonal autoregulation, but not expression by other mechanis
ms, and that a transition from prepattern to autoregulation is necessa
ry for patterning neural cell determination. Distinct neural tissues m
ight differ in their proneural prepatterns, but use Notch in a similar
mechanism. (C) Current Biology Ltd ISSN 0960-9822