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Labial, a Homeotic Gene of The Downloaded from genesdev.cshlp.org on October 7, 2021 - Published by Cold Spring Harbor Laboratory Press Isolation, structure, and expression of labial, a homeotic gene of the . Antennapedia Complex involved m Drosophila head development Robert J. Diederich, Valerie K.L. Merrill, 1 Mary Anne Pultz, 2 and Thomas C. Kaufman Programs in Molecular, Cellular, Developmental Biology, and Genetics, Department of Biology, Indiana University, Bloomington, Indiana 47405 USA The labial (lab) gene of Drosophila melanogaster is necessary for the proper development of the embryonic (larval) and adult head. We have identified the lab transcription unit within the proximal portion of the Antennapedia Complex (ANT-C) by mapping the molecular lesions associated with chromosomally rearranged lab alleles. We present its molecular structure, nucleotide sequence, and temporal pattern of expression. In addition, using antibodies generated against a fusion protein, we show that in the embryo the lab protein is distributed in neural and epidermal cells of the procephalic lobe; in a discrete loop of the midgut; and in specific progenitor sensory cells of the clypeolabrum, thoracic segments, and tail region. The regions of lab expression in the developing cephalon represent nonsegmented domains that are anterior to and largely nonoverlapping with the domains of expression of the Deformed (Dfd) and proboscipedia (pb) genes, two other homeotic loci of the ANT-C that also function to direct the development of head structures. Furthermore, lab head expression is associated with the complex cellular movements of head involution, a process that not only is defective in lab- embryos, but the failure of which appears to be largely responsible for the defects observed in mutant embryos. Finally, we suggest that lab head expression provides a molecular marker for an intercalary segment, an ancestral segment that has become morphologically indistinct during the evolution of the insect head. [Key Words: Antennapedia Complex; Drosophila; head segmentation; homeo box; labial; protein localization] Received December 7, 1988; revised version accepted January 30, 1989. The body plan of Drosophila is composed of a repeating These include bicoid (bed), a maternal-effect gene neces- array of segments, the identities of which are specified sary for the specification of the anterior-posterior axis by the activity of homeotic genes. This role has been of the embryo (Frohnh6fer and Nfisslein-Volhard 1986); inferred from genetic analyses: mutations that lead to fushi tarazu (ftz), a segmentation gene of the pair-rule inactivation or misexpression of a homeotic gene effect class {Wakimoto et al. 1984); and zerknfillt {zen), a zygo- the transformation of one segment to the identity of an- tically active gene required for dorsal embryonic devel- other. Two main clusters of homeotic genes, the Bith- opment (Wakimoto et al. 1984). Molecular analysis has orax Complex (BX-C)[Lewis 1978; SKnchez-Herrero et shown that each of the aforementioned genes contains a al. 1985) and the Antennapedia Complex (ANT-C) homeo box domain (McGinnis et al. 1984; Scott and [Lewis et al. 1980a, b; Kaufman et al. 1980) are found in Weiner 1984; Kuroiwa et al. 1985; Doyle et al. 1986; Fri- the Drosophila genome. The genes of the BX-C are in- gerio et al. 1986; Hoey et al. 1986; Regulski et al. 1987; volved in specifying the identity of thoracic and abdom- Berleth et al. 1988; Mlodzik et al. 1988; D. Cribbs, M.A. inal segments, whereas the homeotic genes of the Pultz, and T.C. Kaufman, in prep.; this paper). An addi- ANT-C direct the development of head and thoracic seg- tional borneo-box-containing gene, z2, for which no ge- ments (for review, see Mahaffey and Kaufman 1988). netic function is known, also has been discovered The ANT-C comprises five homeotic genes: Antenna- within the ANT-C (Rushlow et al. 1987; Pultz et al. pedia (Antp), Sex combs reduced (Scr), Deformed (Dfd), 1988). The isolation of lab, described herein, marks the proboscipedia (pb), and labial {lab; V.K.L. Merrill, R.J. completion of the molecular cloning of the ANT-C. Diederich, F.R. Tumer, and T.C. Kaufman, in prep.). In Thus, in this remarkable portion of the Drosophila addition, genetic analysis has revealed three other loci genome, nine homeo-box-containing genes are clustered that function to establish the embryonic body plan. within -330 kb of contiguous genomic sequence. The lab gene, the most proximal member of the ANT-C, recently has been shown to be necessary for the proper development of the larval and adult head. (A de- tailed developmental genetic analysis will be presented tCurrent address: Biology Department, Brandeis University, Waltham, Massachusetts 02154 USA; 2Current address: Department of Biological elsewhere; V.K.L. Merrill et al. in prep.). To summarize, Sciences, Stanford University, Stanford, California 94305 USA. embryos lacking lab function exhibit a mutant pheno- GENES & DEVELOPMENT 3:399--414 91989 by Cold Spring Harbor Laboratory ISSN 0890-9369/89 $1.00 399 Downloaded from genesdev.cshlp.org on October 7, 2021 - Published by Cold Spring Harbor Laboratory Press Diederich et al. type late in embryogenesis that involves a disruption of previously isolated in this laboratory as a chromosomal the cellular movements associated with head involu- walk {Scott et al. 1983; see also Garber et al. 1983). The tion. These embryos die at the time of hatching and dis- breakpoint of the chromosomal rearrangement, Dfd ax16, play grossly aberrant mouthpart structures, although no defined the zero coordinate in these cloned sequences homeotic phenotype is apparent. However, observations and was later shown to interrupt the Dfd transcription of a hypomorphic allele that produces adult survivors, in unit (Regulski et al. 19871. To characterize molecularly conjunction with clonal analysis studies using the tech- the lab and pb loci, which prior genetic studies had nique of somatic recombination, have allowed us to placed in the proximal ANT-C (Kaufman 1978; Lewis et infer a homeotic role for lab in determining the seg- al. 1980b), we extended the chromosomal walk 60 kb mental identity of the adult head: Clones of lab mutant proximally. Our recent analysis of the pb region spanned cells in posterior regions of the head display a duplica- the genomic interval -50 to - 110 kb (Pultz et al. 1988). tion of dorsal thoracic tissue. Interestingly, this pheno- The remainder of the chromosomal walk, extending to type is similar to that of Dfd- tissue (Merrill et al. 1987). - 144 kb, is shown in Figure 1. Clearly, an understanding of the relationship of lab and The lab gene was localized within the cloned se- Dfd expression, as well as pb expression, will be an es- quences by physically mapping the breakpoints of chro- sential prerequisite to understanding the genetic control mosomal rearrangements that disrupt lab function. The of head development in Drosophila and, perhaps, in in- cytology, parent chromosomes, and method of isolation sects in general. of the chromosomal rearrangements mapped in this In this paper we identify the lab gene within cloned study are described in V.K.L. Merrill et al. (in prep.I and genomic sequences of the ANT-C and present its ge- Pultz et al. (19881. Standard Southem analysis proce- nomic organization and nucleotide and predicted amino dures were employed to map breakpoints {Bender et al. acid sequences. Using antibodies directed against a por- 1983). Briefly, X clones and/or plasmid subclones of ge- tion of the lab protein, we show that lab is the most nomic DNA were hybridized to Southern blots con- anteriorly expressed of the ANT-C homeotic loci and is taining restriction enzyme digests of whole-genome expressed in domains that are not overtly segmented. DNA from mutant and wild-type {parental) flies. Anom- We discuss the correlation of lab expression with lab alous restriction fragments, present in the mutant DNA mutant defects and the implications of this expression but not the parental DNA, allowed us to identify break- in furthering our understanding of the segmental organi- point positions (data not shown; see also Methods). The zation of the insect head. results of the breakpoint mapping are summarized in Figure 1. Results A distal boundary for the lab locus is provided by the chromosomal rearrangement, pb marS, a small deficiency Identification of the lab locus of the pb locus (Pultz et al. 1988) that genetically com- The centromere-distal portion of the ANT-C, extending plements lab function when heterozygous with lab defi- from polytene chromosome bands 84A4,5 to 84B1,2, was cient chromosomes (e.g., Df(3R)Scr; Lewis et al., 1980b). lab vd 1 4 centromere In (3R)lab a76 ; T(3:4)lab vd21 . map8 BB lab vd2 Df(3R) MAP11 > EP BPXBEB XP BE PBXB XbPB X PEXEE X XS XE PEBPP S E ES ESB i i ii i i I ~f II I I I I I I I v i ~1 1,o 13o 12o 11o 3 , 6.9 kb. transcript I -1.0 kb. transcript I s4K6 I I 63A I 57A7 I I 62C5 m, I 45B7 [ I 5666 I Figure l. Molecular organization of the lab region of the ANT-C. (Bottom) The overlapping k clones (Canton S DNA) of the chromo- somal walk. Phages 63A and 62C5 are contiguous with the chromosomal walk of the pb region (Pultz et al. 19881; coordinates (kb) provided under the restriction map have been extended proximally. Restriction enzymes: (B) BamHI; (E) EcoRI; (P) PstI; (S) SalI; (X) XhoI; (Xb) XbaI (only one site shown). {Top) The breakpoints of mutant chromosomes, which identify the lab transcription unit. Open boxes represent deleted portions of the genome; cross-hatching indicates the regions of uncertainty. Although cytologically normal, the lab val and lab v~ alleles are associated with a small deletion (<2 kb) and a transposition (insertion of -600 bp), respectively.
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