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The Drosophila Hox gene, Sex combs reduced (Scr), is required for patterning the larval and adult, labial and prothoracic segments. Fifteen Scr alleles were sequenced and the phenotypes analyzed in detail. Six null alleles were nonsense mutations ([Scr.sup.2], [Scr.sup.4], [Scr.sup.11], [Scr.sup.13], [Scr.sup.13A], and [Scr.sup.16]) and one was an intragenic deletion ([Scr.sup.17]). Five hypomorphic alleles were missense mutations ([Scr.sup.1], [Scr.sup.3], [Scr.sup.5], [Scr.sup.6], and [Scr.sup.8]) and one was a small protein deletion ([Scr.sup.15]). Protein sequence changes were found in four of the five highly conserved domains of SCR: the DYTQL motif ([Scr.sup.15]), YPWM motif ([Scr.sup.3]), Homeodomain ([Scr.sup.1]), and C-terminal domain (CTD) ([Scr.sup.6]), indicating importance for SCR function. Analysis of the pleiotropy of viable Scr alleles for the formation of pseudotracheae suggests that the DYTQL motif and the CTD mediate a genetic interaction with proboscipedia. One allele [Scr.sup.14], a missense allele in the conserved octapeptide, was an antimorphic allele that exhibited three interesting genetic properties. First, [Scr.sup.14]/Df the same phenotype as [Scr.sup.+]/Df. Second, the ability of the [Scr.sup.14] allele to interact intragenetically with Scralleles mapped to the first 82 amino acids of SCR, which contains the octapeptide motif. Third, [Scr.sup.6], which has two missense changes in the CTD, did not interact genetically with [Scr.sup.14]. DOI: 10.1534/genetics.109.100438

Sex Combs Reduced (SCR) activity is proposed to be required cell nonautonomously for determination of tarsus identity, and Extradenticle (EXD) activity is required cell autonomously for determination of arista identity. Using the ability of Proboscipedia to inhibit the SCR activity required for determination of tarsus identity, we found that loss-of-EXD activity is epistatic to loss-of-SCR activity in tarsus vs. arista determination. This suggests that in the sequence leading to arista determination SCR activity is OFF while EXD activity is ON, and in the sequence leading to tarsus determination SCR activity is ON, which turns EXD activity OFF. Immunolocalization of EXD in early third-instar larval imaginal discs reveals that EXD is localized in the nuclei of antennal imaginal disc cells and localized in the cytoplasm of distal imaginal leg disc cells. We propose that EXD localized to the nucleus suppresses tarsus determination and activates arista determination. We further propose that in the mesodermal adepithelial cells of the leg imaginal discs, SCR is required for the synthesis of a tarsus-inducer that when secreted acts on the ectoderm cells inhibiting nuclear accumulation of EXD, such that tarsus determination is no longer suppressed and arista determination is no longer activated.

The mechanisms that regulate the fushi tarazu (ftz)-encoded FTz protein which modulates engrailed (en) and wingless (wg) gene expression were analyzed in Drosophila eggs during oogenesis. Analysis of Drosophila en and wg gene expression during P-element mutagenesis in Drosophila eggs indicated the role of alphaFTz-F1 orphan nuclear receptors in mediating FTz-mediated modulation of en and wg gene expression. On the other hand, the transcriptional activity of the FTz-F1 gene was also modulated by FTz.

The gene product of fushi tarazu (FTZ) has a homeodomain (HD)-independent activity. Ectopic expression of a FTZ protein that lacks half the HD in embryos results in the anti-ftz phenotype. We have characterized this FTZ HD-independent activity further. Ectopic expression of the HD-independent FTZ activity, in the absence of FTZ activity expressed from the endogenous ftz gene, was sufficient to result in the anti-ftz phenotype. Since the anti-ftz phenotype is a first instar larvae composed nearly entirely of FTZ-dependent cuticular structures derived from the even-numbered parasegments, this result suggests that expression of the HD-independent FTZ activity is sufficient to establish FTZ-dependent cuticle. Activation of FTZ-dependent Engrailed (EN) expression and activation of the ftz enhancer were HD-independent. The ftz enhancer element, AE-1, was activated by the HD-independent FTZ activity; however, the ftz enhancer element, AE-BS2CCC, which is the same as AE-I except for the inactivation of two FTZ HD DNA-binding sites, was not. Activation of the ftz enhancer by ectopic expression of FTZ activity was effective only during gastrulation and germ band extension. In the discussion, we propose an explanation for these results.

The Drosophila maxillary palpus that develops during metamorphosis is composed of two elements: the proximal maxillary socket and distal maxillary palp. The HOX protein, Proboscipedia (PB), was required for development of the proximal maxillary socket and distal maxillary palp. For growth and differentiation of the distal maxillary palp, PB was required in the cells of, or close to, the maxillary socket, as well as the cells of the distal maxillary palp. Therefore, PB is required in cells outside the distal maxillary palp for the expression, by some mechanism, of a growth factor or factors that promote the growth of the distal maxillary palp. Both wingless (wg) and hedgehog (hh) genes were expressed in cells outside the distal maxillary palp in the lancinia and maxillary socket, respectively. Both wg and hh were required for distal maxillary palp growth, and hh was required noncell autonomously for distal maxillary palp growth. However, expression of wg-GAL4 and hh-GAL4 during maxillary palp differentiation did not require PB, ruling out a direct role for PB in the regulation of transcription of these growth factors. [ABSTRACT FROM AUTHOR]

In 1932, Müller first used the term "antimorphic" to describe mutant alleles that have an effect that is antagonistic to that of the wild-type allele from which they were derived. In a previous characterization of mutant alleles of the Drosophila melanogaster Hox gene, Sex combs reduced (Scr), we identified the missense, antimorphic allele Scr(14), which is a Ser10-to-Leu change in the N-terminally located, bilateran-specific octapeptide motif. Here we propose that the cause of Scr(14) antimorphy is the acquisition of a leucine zipper oligomerization motif spanning the octapeptide motif and adjacently located protostome-specific LASCY motif. Analysis of the primary and predicted secondary structures of the SCR N-terminus suggests that while the SCR(+) encodes a short, α-helical region containing one putative heptad repeat, the same region in SCR(14) encodes a longer, α-helical region containing two putative heptad repeats. In addition, in vitro cross-linking assays demonstrated strong oligomerization of SCR(14) but not SCR(+). For in vivo sex comb formation, we observed reciprocal inhibition of endogenous SCR(+) and SCR(14) activity by ectopic expression of truncated SCR(14) and SCR(+) peptides, respectively. The acquisition of an oligomerization domain in SCR(14) presents a novel mechanism of antimorphy relative to the dominant negative mechanism, which maintains oligomerization between the wild-type and mutant protein subunits., (Copyright © 2014 Sivanantharajah and Percival-Smith.)