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Ultrabithorax Regulates Genes at Several Levels of the Wing-Patterning Hierarchy to Shape the Development of the Drosophila Haltere

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Ultrabithorax Regulates Genes at Several Levels of the Wing-Patterning Hierarchy to Shape the Development of the Drosophila Haltere Downloaded from genesdev.cshlp.org on September 30, 2021 - Published by Cold Spring Harbor Laboratory Press Ultrabithorax regulates genes at several levels of the wing-patterning hierarchy to shape the development of the Drosophila haltere Scott D. Weatherbee, Georg Halder, Jaeseob Kim, Angela Hudson, and Sean Carroll1 Howard Hughes Medical Institute and Laboratory of Molecular Biology, University of Wisconsin, Madison, Wisconsin 53706 USA Arthropods and vertebrates are constructed of many serially homologous structures whose individual patterns are regulated by Hox genes. The Hox-regulated target genes and developmental pathways that determine the morphological differences between any homologous structures are not known. The differentiation of the Drosophila haltere from the wing through the action of the Ultrabithorax (Ubx) gene is a classic example of Hox regulation of serial homology, although no Ubx-regulated genes in the haltere have been identified previously. Here, we show that Ubx represses the expression of the Wingless (Wg) signaling protein and a subset of Wg- and Decapentaplegic-activated genes such as spalt-related, vestigial, Serum Response Factor, and achaete-scute, whose products regulate morphological features that differ between the wing and haltere. In addition, we found that some genes in the same developmental pathway are independently regulated by Ubx. Our results suggest that Ubx, and Hox genes in general, independently and selectively regulate genes that act at many levels of regulatory hierarchies to shape the differential development of serially homologous structures. [Key Words: Ultrabithorax; haltere; development; Drosophila; serial homology] Received February 6, 1998; accepted March 26, 1998. Arthropods and chordates possess many serially iterated ancestor, with the resulting posterior flight appendages, homologous structures (segments, vertebrae, limbs, etc.) the halteres, being morphologically distinct and reduced that differ in number, morphology, and function be- in size compared to wings. In Drosophila, the Hox gene tween taxa. In both phyla, different Hox genes regulate Ultrabithorax (Ubx) controls the differential develop- the development of initially similar developmental ment between wing and haltere. Ubx is expressed fields into distinct structures, presumably by controlling throughout haltere development but not in the develop- different sets of target genes (Krumlauf 1994; Carroll ing wing (Struhl 1982; Beachy et al. 1985; White and 1995). Differences in gene expression between certain Wilcox 1985a) (Fig. 1C,D). Reduced Ubx function in serial homologs such as the Drosophila leg and antenna imaginal discs or in Ubx mutant clones results in trans- (Wagner-Bernholz et al. 1991) and vertebrate fore- and formation of haltere tissue into wing tissue (Lewis 1963; hindlimb (Peterson et al. 1994; Gibson-Brown 1996) have Morata and Garcia-Bellido 1976; Morata and Kerridge been described. However, the identity of the Hox-regu- 1981; Kerridge and Morata 1982) (Fig. 1E). Total loss of lated target genes and developmental pathways that de- Ubx function in the developing halteres results in the termine the differences in morphology between any ho- complete transformation of halteres to wings, giving rise mologous structures are not known. It is therefore not to a four-winged fly (Lewis 1978) (Fig. 1F). Conversely, known whether Hox genes act upon a few genes at the mutations that cause ectopic expression of Ubx in the top of, or upon many genes throughout the gene hierar- developing wing disc [e.g., Contrabithorax (Cbx)] (Ca- chies that govern the formation and patterning of ho- brera et al. 1985; White and Akam 1985; White and Wil- mologous structures. cox 1985b; Castelli-Gair et al. 1990) transform wing into Here, we examine the Hox-regulated gene hierarchy haltere tissue (Lewis 1955, 1978, 1982; Morata and governing the differential development of the serially ho- Lawrence 1975; Casanova et al. 1985; Micol and Garcı´a- mologous dipteran (two-winged insects) wing and hal- Bellido 1988; Gonza´lez-Gaita´n et al. 1990). Although tere (Fig. 1A,B). Dipterans evolved from a four-winged these spectacular Ubx mutant phenotypes have been known for decades, no Ubx-regulated genes in the hal- 1Corresponding author. tere have been identified. E-MAIL [email protected]; FAX (608) 262-9343. Recent progress in understanding the genetic mecha- 1474 GENES & DEVELOPMENT 12:1474–1482 © 1998 by Cold Spring Harbor Laboratory Press ISSN 0890-9369/98 $5.00; www.genesdev.org Downloaded from genesdev.cshlp.org on September 30, 2021 - Published by Cold Spring Harbor Laboratory Press Hox genes and serial homology lected Dpp- and Wg-activated target genes or cis-regula- tory elements, and genes that are further downstream of Ubx-regulated genes. We also examined whether the ec- topic expression of these genes was sufficient to induce wing-like characters on the haltere. Our findings reveal that Ubx represses haltere development by indepen- dently regulating selected genes that act at different lev- els of the wing patterning hierarchy. Results The anteroposterior axis: Ubx represses selected Dpp target genes The expression pattern of en is essentially the same in the haltere disc as in the wing disc (Fig. 2A,B), indicating that Ubx is not regulating haltere identity by altering the expression of this compartmental selector gene. Similarly, the expression of dpp in the developing haltere on the an- terior side of the AP compartment boundary resembles that in the wing disc (Fig. 2A,B). Because these discs give rise to very different appendages, there may be genes down- Figure 1. Ubx controls the differential development of the hal- stream of the Dpp signal that are regulated by Ubx. To tere. The wild-type wing (A) and haltere (B) differ in size, shape, identify these, we examined how a number of genes in- and the presence of veins and margin bristles. (C,D) antibody staining of third instar wing and haltere discs. (C) Ubx expres- volved in the development of specific wing characters are sion (red) in the wing disc is limited to the peripodial membrane expressed and regulated in the developing haltere. and is not necessary for proper wing development (Struhl 1982). Dpp acts as a morphogen from its source to organize (D) Ubx expression fills the haltere disc, with strongest expres- wing growth, AP pattern, and to activate target gene ex- sion in the ‘‘pouch’’, which will give rise to capitellar tissue pression over a distance. The optomotor blind (omb), (Beachy et al. 1985). Reduction of Ubx activity in the halteres spalt (sal), and spalt related (salr) genes are expressed in leads to transformations toward wing identity. (E) Haltere from nested patterns centered on the Dpp stripe and are nec- 6.28 34E a Ubx /bx fly (Kerridge and Morata 1982), in which Ubx essary for proper development of the central wing region gene activity is <50% of wild-type (shown at the same magni- including veins II–IV (de Celis et al. 1996; Grimm and fication as B). A large number of ectopic margin bristles appear Pflugfelder 1996; Lecuit et al. 1996; Nellen et al. 1996; on the haltere, which is increased in size. (F) Total loss of Ubx activity in the developing haltere results in a complete trans- Sturtevant et al. 1997). We examined the expression of formation toward wing identity (Lewis 1978). Black scale bars, these Dpp target genes in the haltere disc and found that 0.25 mm; white scale bars, 0.2 mm. although omb is expressed in the developing haltere pouch straddling the Dpp stripe as it does in the wing disc (Fig. 2C), salr and sal are not expressed in the haltere nisms that govern the formation and patterning of the pouch (Fig. 2D; data not shown). These results show that insect wing has created the opportunity to identify genes the Dpp signal transduction machinery operates in the that are regulated differently between wings and hal- haltere disc but that selected wing target genes are not teres. In the Drosophila wing disc, growth and patterning activated by the Dpp signal. are organized by the Decapentaplegic (Dpp) and Wingless To determine whether Ubx represses salr expression (Wg) long-range signaling proteins (for review, see Ser- in the haltere disc, we generated homozygous Ubx− rano and O’Farrell 1997), which are produced by cells clones. Indeed, salr is derepressed in Ubx− clones in the along the anteroposterior (AP) and dorsoventral (DV) anterior compartment of the haltere disc. As in the wing compartment boundaries, respectively, and organize disc, salr expression in these clones depended on their growth and patterning via the regulation of numerous distance from the Dpp source (Fig. 2E). To determine downstream wing-patterning target genes. The expres- whether Ubx is sufficient to repress salr, we examined sion of Dpp and Wg is regulated by the short-range sig- salr expression in CbxM1/+ wing discs in which Ubx is naling proteins Hedgehog (Hh) and Serrate (Ser), which ectopically expressed along part of the DV boundary. In are in turn regulated by the posterior engrailed (en) and these wing discs salr expression is repressed in a cell dorsal apterous (ap) selector genes (for review, see Burke autonomous fashion (Fig. 2F). Because sal/salr are re- and Basler 1997; Irvine and Vogt 1997; Neumann and quired for the induction of vein development (Sturtevant Cohen 1997a). et al. 1997), the selective repression of salr by Ubx sup- We have investigated how Ubx modifies a wing field presses part of the Dpp-mediated AP wing patterning into a haltere field by focusing on these global signaling program in the haltere. systems and their target genes. We discovered that Ubx As with the spatial patterning of wing veins, the pat- regulates the expression of the Wg signaling protein, se- tern of intervein tissue is also determined by specific GENES & DEVELOPMENT 1475 Downloaded from genesdev.cshlp.org on September 30, 2021 - Published by Cold Spring Harbor Laboratory Press Weatherbee et al.
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