The transcriptional co-factor Chip acts with LIM-homeodomain proteins to set the boundary of the eye field in Drosophila

Abstract

SUMMARYDevelopment involves the establishment of boundaries between fields specified to differentiate into distinct tissues. The Drosophila larval eye-antennal imaginal disc must be subdivided into regions that differentiate into the adult eye, antenna and head cuticle. We have found that the transcriptional co-factor Chip is required for cells at the ventral eye-antennal disc border to take on a head cuticle fate; clones of Chip mutant cells in this region instead form outgrowths that differentiate into ectopic eye tissue. Chip acts independently of the transcription factor Homothorax, which was previously shown to promote head cuticle development in the same region. Chip and its vertebrate CLIM homologues have been shown to form complexes with LIM-homeodomain transcription factors, and the domain of Chip that mediates these interactions is required for its ability to suppress the eye fate. We show that two LIM-homeodomain proteins, Arrowhead and Lim1, are expressed in the region of the eye-antennal disc affected in Chip mutants, and that both require Chip for their ability to suppress photoreceptor differentiation when misexpressed in the eye field. Loss-of-function studies support the model that Arrowhead and Lim1 act redundantly, using Chip as a co-factor, to prevent retinal differentiation in regions of the eye disc destined to become ventral head tissue.

Competition among gene regulatory networks imposes order within the eye-antennal disc of Drosophila

“…As previously stated, these anteriormost cells give rise to head capsule tissue (Haynie and Bryant, 1986) and express both ct and Lim1 (Fig. 2B-D, arrows) (Blochlinger et al, 1993;Tsuji et al, 2000;Roignant et al, 2010). In normal development, Ey protein is not co-distributed with either of these two factors ( Fig.…”

“…In normal development, Ey protein is not co-distributed with either of these two factors ( Fig. 2A-C) and this has led to a model in which Ct and Lim1 repress ey transcription and vice versa (Kenyon et al, 2003;Roignant et al, 2010). We find that Ct and Lim1 proteins are found within the eya 2 mutant eye disc ( Fig.…”

“…Similar to these examples, Awh 1 mutants are characterized by a dramatic reduction in the overall size of the disc and deficits in the expression of genes that regulate furrow progression and photoreceptor development (Curtiss and Heilig, 1995). It has been proposed that the loss of retinal tissue in Awh 1 is due to a block in retinal precursor cell formation and not to developmental cell death as in eya 2 mutants (Curtiss and Heilig, 1995 (Bodmer et al, 1987;Royet and Finkelstein, 1995;Royet and Finkelstein, 1996;Royet and Finkelstein, 1997;Tsuji et al, 2000;Kenyon et al, 2003;Tomlinson, 2003;Roignant et al, 2010). Although ey is expressed within a broad zone ahead of the morphogenetic furrow its transcription is silenced in the swath of cells within the eye disc that borders the antennal disc ( Fig.…”

“…Consistent with these effects, loss of either homothorax (hth) or extradenticle (exd) within the head capsule leads to the formation of ectopic eyes (González-Crespo and Morata, 1995;Rauskolb et al, 1995;Pai et al, 1998;Pichaud and Casares, 2000). Likewise, overexpression within the eye field of Arrowhead (Awh), a LIM-type homeodomain transcription factor that is important for the formation of ventral head capsule, leads to replacement of the retina with head capsule (Curtiss and Heilig, 1995;Curtiss and Heilig, 1997;Roignant et al, 2010). The loss of retinal tissue is thought to be in part due to a block in retinal precursor cell formation and a downregulation of eyepromoting genes.…”

Chip physically interacts with Notch and their stoichiometry is critical for Notch function in wing development and cell proliferation in Drosophila

“…and Chip form a functional complex, which is a tetramer formed by two Ap molecules bridged by two Chip molecules, was established [25,27,28,30]. Chip has also been reported for regulating axon guidance [31], posteclosion behavior [32], and establishing the boundary of the eye field [33] in Drosophila.…”