We have isolated a new Drosophila mutant, satori (sat), the males of which do not court or copulate with female flies. The sat mutation comaps with fruitless (fru) at 91B and does not rescue the bisexual phenotype of fru, indicating that sat is allelic to fru (frusae). The frusat adult males lack a male-specific muscle, the muscle of Lawrence, as do adult males with otherfru alleles. A powerful approach to investigating the biological basis of sexual orientation is to use animal models that allow experimental manipulation of complex behavior. Drosophila melanogaster provides the combination of identified neurons of known projection, the applicability of classic genetic theory, and the potential for advanced molecular biological analysis, making it an excellent organism for investigating higher neural functions such as sexual orientation (1-4). We have screened about 2000 fly lines with single P-element insertions for altered sexual behavior, yielding a mutant named satori (sat; nirvana in Japanese), the males of which do not court or copulate with females. Instead, sat males exhibit homosexual courtship. We report here that sat is allelic to fruitless (fru) whose dysfunction is known to lead to "bisexual" behavior (5-7) and loss of a male-specific muscle, the muscle of Lawrence (MOL) (8,9). We further show that frusat is a likely transformer (tra) target, encodes a putative transcription factor with a BTB domain (10) and two zinc finger motifs, and is expressed in a subset of cells in the central nervous system. PlwB element as a mutator and the P (ry+A2-3) transposon as a jump starter. All flies used in the mutagenesis had a white-(w-) background, whereas the PlwB element carried a copy of w+, allowing us to recover chromosomes with PlwB insertions by selecting individuals with nonwhite eye color. After establishing fly lines with new insertions, homozygous virgin males and females were collected at eclosion, placed singly in food vials, and aged for 3 days. For behavior screening, single male and female pairs were introduced into disposable plastic syringes (volume, 1 cm3). At least 10 pairs per strain were visually observed for 1 h, and the time to copulation, duration of copulation, and percentage of pairs copulating were recorded. In this screen, we isolated seven mutations, sat, croaker (cro) (11), fickle, okina, spinster (7), chaste, and lingerer (see ref. 4 for further details of these mutations). By introducing the P (ry+A2-3) chromosome to the sat line, the mutator element was remobilized, resulting in approximately 50 lines with white eyes. sat15 and satr2 are representative of these lines: sat15 is lethal when expressed homozygously and induces mutant phenotypes when expressed heterozygously with sat, whereas sat'2 does not induce mutant phenotypes. We consider satr2 to be a revertant because precise excision of the

Mutations in the spin gene are characterized by an extraordinarily strong rejection behavior of female flies in response to male courtship. They are also accompanied by decreases in the viability, adult life span, and oviposition rate of the flies. In spin mutants, some oocytes and adult neural cells undergo degeneration, which is preceded by reductions in programmed cell death of nurse cells in ovaries and of neurons in the pupal nervous system, respectively. The central nervous system (CNS) of spin mutant flies accumulates autofluorescent lipopigments with characteristics similar to those of lipofuscin. The spin locus generates at least five different transcripts, with only two of these being able to rescue the spin behavioral phenotype; each encodes a protein with multiple membrane-spanning domains that are expressed in both the surface glial cells in the CNS and the follicle cells in the ovaries. Orthologs of the spin gene have also been identified in a number of species from nematodes to humans. Analysis of the spin mutant will give us new insights into neurodegenerative diseases and aging.

Synoviolin, also called HRD1, is an E3 ubiquitin ligase and is implicated in endoplasmic reticulum -associated degradation. In mammals, Synoviolin plays crucial roles in various physiological and pathological processes, including embryogenesis and the pathogenesis of arthropathy. However, little is known about the molecular mechanisms of Synoviolin in these actions. To clarify these issues, we analyzed the profile of protein expression in synoviolinnull cells. Here, we report that Synoviolin targets tumor suppressor gene p53 for ubiquitination. Synoviolin sequestrated and metabolized p53 in the cytoplasm and negatively regulated its cellular level and biological functions, including transcription, cell cycle regulation and apoptosis. Furthermore, these p53 regulatory functions of Synoviolin were irrelevant to other E3 ubiquitin ligases for p53, such as MDM2, Pirh2 and Cop1, which form autoregulatory feedback loops. Our results provide novel insights into p53 signaling mediated by Synoviolin.

Summary Epidermal cell migration is critical for restoration of tissue structure and function after damage [1]. However, the mechanisms by which differentiated cells neighboring the wound sense the wound and assume a motile phenotype remain unclear. Here we show that Pvr, a receptor tyrosine kinase (RTK) related to platelet derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) receptors, and one of its ligands, Pvf1, are required for epidermal wound closure. Morphological comparison of wound-edge cells lacking Pvr or the Jun N-terminal kinase (JNK) signaling pathway previously implicated in larval wound closure [2] suggests that Pvr signaling leads wound margin epidermal cells to extend actin-based cell processes into the wound gap while JNK mediates transient dedifferentiation of cells at the wound margin. Genetic epistasis experiments reinforce the conclusion that the JNK and Pvr signaling pathways act in parallel. Tissue-specific knockdown and rescue experiments suggest that epidermally-derived Pvf1 may be sequestered in the blood and that tissue damage exposes blood-borne Pvf1 to Pvr receptors on wound-edge epidermal cells and initiates the extension of cell processes into the wound gap. These results uncover a novel mechanism of sensing tissue damage and suggest that PDGF/VEGF ligands and receptors may have a conserved autocrine role in epidermal wound closure.