Negative regulation of atonal in proneural cluster formation of Drosophila R8 photoreceptors

Abstract

atonal (ato) encodes a basic helix-loop-helix protein and is required for the specification of R8 photoreceptor cells in Drosophila. In the eye imaginal discs, expression of Ato protein is initially in a dorsoventral stripe of cells anterior to the morphogenetic furrow (MF). In the MF, this stripe expression is resolved into regularly spaced clusters of Ato-positive cells, the proneural clusters, which are intervened with Ato-negative cells. Another basic helix-loop-helix protein, Daughterless (Da), dimerizes with Ato and is expressed at an enhanced level in Ato-expressing cells. Here we show that during the late stages of proneural clusters, the mitogen-activated protein kinase (MAPK) is activated in proneural clusters. Normal ato or da activity is required for maintenance of MAPK activation. Furthermore, in ato or da mutants, Ato expression is expanded to all cells in the MF, suggesting that ato and da are required for Ato repression in cells between proneural clusters. By changing the MAPK activity in proneural clusters, we show that MAPK activation mediates Ato repression nonautonomously. Consistently, hyperactivation of the MAPK in a stripe of cells posterior to or overlapping the Ato stripe eliminates the formation of proneural clusters. Taken together, these results suggest that a negative regulatory loop involving MAPK activation and Ato repression is required for the generation of evenly spaced proneural clusters.

Identification of Novel Regulators of atonal Expression in the Developing Drosophila Retina

“…Increased nuclear translocation of MAP kinase, a downstream component of the Egfr pathway, has been shown to disrupt Atonal protein expression and spacing (Kumar et al 2003;, and increased Egfr expression directed within the morphogenetic furrow also shows decreased Atonal expression (Chen and Chien 1999). Further, a gain-offunction mutation in Egfr (Egfr…”

Echinoid limits R8 photoreceptor specification by inhibiting inappropriate EGF receptor signalling within R8 equivalence groups

“…ed does not completely suppress Egfr signalling around the morphogenetic furrow, presumably because such signalling has some role to play. Indeed this wild-type level of signalling may be important for mediating the proposed inhibitory Egfr/Ras/Raf process in which one row of IGs helps to pattern the next row (Chen and Chien, 1999;Baonza et al, 2001;Yang and Baker, 2001) (Fig. 7).…”

“…Mutations in genes involved in this process result in irregular and denser IG spacing, as is seen for the secreted molecule Scabrous (Sca) (Ellis et al, 1994). A number of studies have implicated Egfr/Raf/Ras signalling in IG spacing, possibly in cooperation with Notch (Dominguez et al, 1998;Spencer et al, 1998;Chen and Chien, 1999;Baonza et al, 2001), although this conclusion is not universally accepted (Kumar et al, 1998).…”

“…5C,E). Clearly, such signalling does not normally interfere with R8 equivalence group resolution; it may mediate a proposed function of Egfr signalling during IG spacing (Dominguez et al, 1998;Spencer et al, 1998;Chen and Chien, 1999;Lesokhin et al, 1999;Yang and Baker, 2001). In ed mutant eye discs, the patterns of pnt-P1 and dpErk are unchanged, but the levels of both are elevated in the IGs and equivalence groups (Fig.…”

“…This is true of Epidermal Growth Factor Receptor (Egfr) signalling, which plays diverse roles during Drosophila melanogaster eye development (e.g. Freeman, 1996;Dominguez et al, 1998;Chen and Chien, 1999;Baonza et al, 2001). Often these different roles seem spatially and temporally to be overlapping, raising questions of how distinct cellular responses are regulated.…”