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Ectopic Expression of the Drosophila Homeotic Gene Proboscipedia Under Antennapedia P1 Control Causes Dominant Thoracic

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Ectopic Expression of the Drosophila Homeotic Gene Proboscipedia Under Antennapedia P1 Control Causes Dominant Thoracic Copyright 0 1992 by the Genetics Society of America Ectopic Expression of the Drosophila Homeotic Geneproboscipedia Under Antennapedia P1 Control Causes Dominant Thoracic Defects David L. Cribbs,’ Angela M. Pattatucci,2 Mary Anne Pultz’ and Thomas C. Kaufman Howard Hughes Medical Institute, Institutefor Cellular and MolecularBiology, and Programs an Genetics and Cellular, Molecular and Developmental Biology, Department of Biology, Indiana University, Bloomington 47405 Manuscript received May 13, 1992 Accepted for publication July 17, 1992 ABSTRACT A deletion mutation in theAntennapedia Complex of Drosophilamelanogaster, Df(3R)SCBXL2, induces both dominant and recessive loss-of-function phenotypes. The deletion is associated with diminished function of proboscipedia (pb), a homeotic gene required for mouthparts formation. Df(3R)SCBXL2also has associated dominant thoracic defects related to diminished expression of the homeotic Antennapedia (Antp) gene copy on the homologous chromosome. This is shown to be a consequence of ectopic pb expression in the thorax. Newly juxtaposed Antp sequences provide thepb gene on the deletion bearing chromosomewith a second promoter, Antp P1, in addition to its own. Ectopic pb protein expression occurs under Antp PI control, by alternate splicing, and results in diminished accumulationofAntp protein in the imaginal disc cellswhere Antp P1 is normally expressed. The analysis of this mutant chromosome thus demonstrates thatpb protein is capable of participating in the negative regulationof a more posteriorly expressedhomeotic gene, as well as servinga homeotic “selector” function in the head. HE fruit fly Drosophila melanogaster is composed ROLL et al. 1986). In contrast in the head it appears T of a series of related but distinct segments or that the homeoticgenes are expressed in nonoverlap- parasegments. These reiterated pattern elements, the ping regions and that these exclusive domains do not outcome of a series of tightly coupled events in early resultfrom negative cross regulatoryinteractions embryogenesis [see AKAM 987)(1 and INGHAM (1 988) (MAHAFFEY,DIEDERICH and KAUFMAN1989; KAUF- for reviews], definethe domains of action of the MAN, SEEGERand OLSEN 1990). homeotic genes. The diversification of structures dis- The homeotic proboscipedia (fib) gene of the ANT- tinguishing one segment from another is believed to C is required to make adult mouthparts. Inits absence reflect homeotic gene regulatory functions directed a transformation of the labial palps to prothoracic legs toward “downstream” or “realisator” genes (GARCIA- occurs (BRIDGESand DOBZHANSKY1933; KAUFMAN BELLIDO1977; LEWIS1978; GOULDet al. 1990). In 1978; PULTZet al. 1988). A distinctly different adult Drosophila there are two major clusters of homeotic transformation of the labial palps to antennal aristae genes, the Bithorax Complex (BX-C) and the Anten- is seen in mutants which retain partial pb function. napedia Complex (ANT-C), which together control Consistent with the adult mutant phenotype, larval the segmental identity of most of the fly body [for expression of pb protein is detected in cells of the reviews, see PEIFER,KARCH and BENDER (1987), DUN- labial imaginal discswhich formthe adult labium CAN (1987), MAHAFFEYand KAUFMAN(1988), and (RANDAZZO,CRIBBS and KAUFMAN199 1). Embryonic KAUFMAN,SEEGER and OLSEN (1990)l.The genes of expression of pb protein is also observed in the labial the BX-C are required for specification of posterior and maxillary lobes of the gnathocephalon. These two thoracic and abdominal segments, while those of the segments are thelikely site of origin of the progenitor ANT-C are required in the anterior thorax and the cells of theadult head which are affected in pb- head. In the trunk, homeotic genes are expressed in animals (PULTZet al. 1988; JURGENS et al. 1986). overlapping domains and may interact among them- However, no embryonic or larval cuticular phenotype selves at thetranscriptional level to alter one another’s has been associated with the pb- condition (PULTZet pattern of expression (STRUHL1982; HAFEN,LEVINE al. 1988). and GEHRING 1984; STRUHL andWHITE 1985; CAR- The Antennapedia (Antp) gene of the ANT-C, in contrast, is required for mesothoracic identity both in ’ Present address: Centre de Biologie du Dkveloppement, Bitiment 4B3, 1 18 route de Narbonne, 3 1062 Toulouse Cedex,France. embryonic/larval and adult development (WAKIMOTO ‘ Present address: Laboratory of Biochemistry, Building 37, Room 4A13, and KAUFMAN 1981;STRUHL 1981; ABBOTTand National Institutes of Health, Bethesda, Maryland 20892. ’ Present address: Department of Biology, Western Washington Univer- KAUFMAN1986; MARTINEZ-ARIAS 1986).The Antp sity, Bellingharn, Washington 98225. protein is apparently sufficient to specify mesothoracic Genetics 132: 699-71 1 (November, 1992) 700 L. D. Cribbs et al. identity; a conclusion drawn from genetic and molec- otherwise noted. Mutant strains and nomenclature are as in ular analyses of dominant gain-of-function Antp mu- LINDSLEYand ZIMM (1992).The Df(3R)SCBxL2chromosome was supplied by C. NUSSLEIN-VOLHARDand was recovered tations which transform head tissues to mesothorax in her laboratory as a deletion of the bicoid (bcd) locus of (e.g., see DENELL1973; HAZELRIGG and KAUFMAN the ANT-C. This deletion also removes the Antp, fushi 1983; FRISCHER, HACEN and GARBER1986; tarazu (ftz),Sex combs reduced (Scr),Deformed (Dfd),Amalgam SCHNEUWLY,KUROIWA and GEHRING1987; (AMA), and zerknullt (zen) loci as well as showing a partial SCHNEUWLY,KLEMENZ and GEHRING 1987).Antp also and variegating loss-of-function phenotype for the pb locus. In addition to the recessive lethal effects of the deletion it contributes to adult development of the prothorax, is associated with a dominant phenotype most readily seen notably the humeral callus and the mesonotum (AB- as a deletion of bristles and cuticle in the region of the BOTT and KAUFMAN1986). Two distinct promoters, humeral callus. This dominant effect closely resembles re- P1 and P2, direct Antp expression (LAUCHONet al. cessive loss-of-function phenotypes associated with certain 1986; SCHNEUWLYet al. 1986; STROEHER,JORGENSON alleles of the Antp locus (ABBOTTand KAUFMAN1986). Geneticreversion analysis: Males of genotype and GARBER 1986;JORGENSON and GARBER 1987). Df(3R)SCBXL2/TM3,Sbwere placed overnight (about 16 hr) Whereas P2 is necessary from embryogenesis onwards in vials containing tissues wetted with 10% sucrose solution/ and is required in the ventral thorax, theP 1promoter 6 mM diepoxybutane (DEB) (OLSENand GREEN1982), or is required for adult viability and for proper devel- with ethyl methanesulfonate (EMS) using standard condi- opment of dorsal thoracic structures (WAKIMOTOand tions (BACHERand LEWIS1968). Males were then removed to fresh vials, allowed several hours to recover, then mated KAUFMAN1981; STRUHL 1981; ABBOTTand KAUF- with virgin pb‘”pp females. The weak pbI3 allele in combi- MAN 1986). nation with Df(3R)SCBXLZonly rarely gives a phenotype Loci homologous to the homeotic genes of the BX- which is visible under a dissecting microscope. F, progeny C and the ANT-C are united in a single complex in carrying the deficiency chromosome (i.e., Sb+)were screened various species including the flour beetle Tribolium for reversion of the humeral defects, and for labial defects indicating the introduction of a pb lesionon the castaneum, mice and humans (BEEMAN 1987; BEEMAN Df(3R)SCBXL2chromosome. The humeral defects associated et al. 1989; DUBOULEand DOLL^? 1989;GRAHAM, withthis chromosome were thoughtto becaused by a PAPALOPULUand KRUMLAUF1989; ACAMPORAet al. negative regulation of the Antp locus resident on the ho- 1989; KAPPEN, SCHUGHARTand RUDDLE 1989).The mologous chromosome. Thus “reversion” of the dominant protein products of the homeotic genes are seen to be phenotype should be associated with the inactivation of the entity on the deletion chromosome causing the shut down. potent developmental effectors through their known Candidates expressing either phenotype were recrossed to or inferred activities as transcriptional regulators.The pb” Pp to confirm the introduction of a new pb lesion and/ extraordinary conservationof the homeotic genecom- or a reversion and then balanced over TM3,Sb. The DEB- plexes seems likely to reflect a necessity to maintain a induced alleleswere first tested for complementation of fine balance of the homeotic genes’ functions and lethal labial mutations, the next most proximal member of the ANT-C, and stronger alleles of fib. The DEB induced hence their spatial, temporal and quantitative expres- alleles were also mapped by genomic Southern blots. The sion for proper development. A knowledge of what mutation frequency observed with DEB for pb was about interactions may comprise homeotic gene regulation, 0.02%and EMS was similarly efficient; hence the expected and how such interactions may be modulated, is thus frequency of chromosomes doubly hit at pb and any other central to our understanding of developmental con- second site should be on the order of 4 X Gene dosagetests: To vary the dosage of Antp+, an trol. additional copy of the ANT-C was introduced via the Y This paperdeals with the regulation of Antp expres- chromosome using Dp(Y;3)ANT-C+(a Y chromosome-linked sion by the pb locus of the ANT-C. We have analyzed translocation of the entire ANT-C, duplicated for polytene a deficiency mutation in which the Antp P1 promoter region 83DE-84D; obtained by R. DENELL,Kansas State is placed upstream of the
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