Search

Roberto Gallego-Pinazo1,2, Ana Marina Suelves-Cogollos1, Rosa Dolz-Marco1, J Fernando Arevalo3, Salvador García-Delpech1, J Luis Mullor4, Manuel Díaz-Llopis1,2,51Department of Ophthalmology, Hospital Universitario La Fe, Valencia, Spain; 2Centro de Investigación Biomédica en Red de Enfermedades Raras, Valencia, Spain; 3Retina and Vitreous Service, Clinical Ophthalmology Center, Caracas, Venezuela; 4Unit of Experimental Ophthalmology, Hospital Universitario La Fe, Valencia, Spain; 5University of Valencia, Faculty of Medicine, Valencia, SpainBackground: The aim of this study was to compare the efficacy of spectral-domain optical coherence tomography (SD-OCT) and fluorescein angiography (FA) in the guidance of macular laser photocoagulation for diabetic macular edema.Methods: This was a prospective interventional clinical comparative pilot study. Forty eyes from 24 consecutive patients with diabetic macular edema were allocated to receive laser photocoagulation guided by SD-OCT or FA. Best-corrected visual acuity (BCVA), central macular thickness, and retinal volume were assessed at baseline and two months after treatment.Results: Subjects treated using FA-guided laser improved BCVA from the logarithm of the minimum angle of resolution (logMAR) 0.52 ± 0.2 to 0.37 ± 0.2 (P < 0.001), and decreased mean central macular thickness from 397.25 ± 139.1 to 333.50 ± 105.7 µm (P < 0.001) and retinal volume from 12.61 ± 1.6 to 10.94 ± 1.4 mm3 (P < 0.001). Subjects treated using SD-OCT guided laser had improved BCVA from 0.48 ± 0.2 to 0.33 ± 0.2 logMAR (P < 0.001), and decreased mean central macular thickness from 425.90 ± 149.6 to 353.4 ± 140 µm (P < 0.001) and retinal volume from 12.38 ± 2.1 to 11.53 ± 1.1 mm3 (P < 0.001). No significant differences between the groups were found in two-month BCVA (P = 0.505), two-month central macular thickness (P = 0.660), or two-month retinal volume (P = 0.582).Conclusion: The short-term results of this pilot study suggest that SD-OCT is a safe and effective technique and could be considered as a valid alternative to FA in the guidance of macular laser photocoagulation treatment for diabetic macular edema.Keywords: spectral-domain optical coherence tomography, fluorescein angiography, macular laser photocoagulation, diabetic macular edema

A growing market for seaweed products has emerged in the last 20 years, with microalgae and their extracts representing a source of high-value chemicals. In this study, antioxidative and anti-inflammatory activities of lipid fraction extract from Chlorella vulgaris (Chlorella) and Arthrospira platensis (Spirulina) on Normal Human Dermal Fibroblasts (NHDF cells) were evaluated. Treatments with Chlorella and Spirulina lipid extracts in NHDF cells at 0.1, 0.5, and 1% significantly protect UVA-induced damage by decreasing oxidative stress in the form of reactive oxygen species (ROS) but do not display any significant protection from HEV-induced damage. Chlorella or Spirulina lipid extracts at 0.1 and 0.5% display significant anti-inflammatory effects by inhibiting the 2-propanol-induced IL-6 expression on NHDF cells in vitro but showed no decrease in TNF-α expression. Chlorella and Spirulina lipid extracts present antioxidant and anti-inflammatory activity on NHDF cells., Competing Interests: DECLARATION OF CONFLICTING INTERESTSThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Collagen is one of the major proteins of the skin and it is particularly important for its strength and resilience. Skin aging is a natural process that is characterized by the decrease and fragmentation of collagen in the dermis. Oral supplementation with collagen peptides has been clinically shown to have a positive effect on the skin condition. However, the mechanisms of aging-related changes synthesized by cells exposed to collagen are currently not well understood. Therefore, in this in vitro study, the mechanisms associated with collagen, elastin, and versican in human dermal fibroblasts were investigated after exposure to collagen peptides., Methods: The effects of different concentrations of collagen peptides on cell viability and metabolism were analyzed. For gene expression analysis, human dermal fibroblasts were treated with collagen peptides. This was then followed by RNA extraction and DNA synthesis. Gene expressions of collagen type 1 (COL1A1), elastin (ELN), and versican (VCAN) were quantified by quantitative reverse transcription polymerase chain reaction (RT-qPCR). In addition, collagen levels were analyzed by confocal scanning laser microscopy using immunostaining., Results: Collagen peptides tested in the study increased the expression of the relevant COL1A1, ELN, and VCAN genes in human dermal fibroblasts ( p  < 0.005). Furthermore, confocal microscopy showed increased collagen expression in the dermal fibroblast culture after treatment with the collagen peptides ( p  < 0.005)., Conclusion: These data provide cell-based evidence for the beneficial effects of exposure to collagen peptides on the skin's collagen content and on the molecules that provide firmness and elasticity. This may support the hypothesis that collagen peptides are important for maintaining extracellular matrix (ECM) structure and skin regeneration., Competing Interests: MP and RN-U were employed by PB Leiner, part of Tessenderlo Group NV. SD, MP, and RN-U are working for the funding stakeholder. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dierckx, Patrizi, Merino, González, Mullor and Nergiz-Unal.)

Air pollution is a growing threat to human health. Airborne pollution effects on respiratory, cardiovascular and skin health are well-established. The main mechanisms of air-pollution-induced health effects involve oxidative stress and inflammation. The present study evaluates the potential of a polyphenol-enriched food supplement ingredient comprising Lippia citriodora , Olea europaea , Rosmarinus officinalis , and Sophora japonica extracts in mitigating the adverse effects of environmental pollution on skin and cardiopulmonary systems. Both in vitro and ex vivo studies were used to assess the blend's effects against pollution-induced damage. In these studies, the botanical blend was found to reduce lipid peroxidation, inflammation (by reducing IL-1α), and metabolic alterations (by regulating MT-1H, AhR, and Nrf2 expression) in human skin explants exposed to a mixture of pollutants. Similar results were also observed in keratinocytes exposed to urban dust. Moreover, the ingredient significantly reduced pollutant-induced ROS production in human endothelial cells and lung fibroblasts, while downregulating the expression of apoptotic genes (bcl-2 and bax) in lung fibroblasts. Additionally, the blend counteracted the effect of urban dust on the heart rate in zebrafish embryos. These results support the potential use of this supplement as an adjuvant method to reduce the impact of environmental pollution on the skin, lungs, and cardiovascular tissues.

Huntington's disease (HD) is an inherited neurodegenerative disorder considered a rare disease with a prevalence of 5.7 per 100,000 people. It is caused by an autosomal dominant mutation consisting of expansions of trinucleotide repeats that translate into poly-glutamine enlarged mutant huntingtin proteins (mHTT), which are particularly deleterious in brain tissues. Since there is no cure for this progressive fatal disease, searches for new therapeutic approaches are much needed. The small molecule pytren-4QMn (4QMn), a highly water-soluble mimic of the enzyme superoxide dismutase, has shown in vivo beneficial anti-inflammatory activity in mice and was able to remove mHTT deposits in a C. elegans model of HD. In this study, we assessed 4QMn therapeutic potential in zQ175 neo-deleted knock-in mice, a model of HD that closely mimics the heterozygosity, genetic injury, and progressive nature of the human disease. We provide evidence that 4QMn has good acute and chronic tolerability, and can cross the blood-brain barrier, and in male, but not female, zQ175 mice moderately ameliorate HD-altered gene expression, mHtt aggregation, and HD disease phenotype. Our data highlight the importance of considering sex-specific differences when testing new therapies using animal models and postulate 4QMn as a potential novel type of small water-soluble metal complex that could be worth further investigating for its therapeutic potential in HD, as well as in other polyglutamine diseases.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder, of the so-called minority diseases, due to its low prevalence. It is caused by an abnormally long track of glutamines (polyQs) in mutant huntingtin (mHtt), which makes the protein toxic and prone to aggregation. Many pathways of clearance of badly-folded proteins are disrupted in neurons of patients with HD. In this work, we show that one Mn(II) quinone complex (4QMn), designed to work as an artificial superoxide dismutase, is able to activate both the ubiquitin-proteasome system and the autophagy pathway in vitro and in vivo models of HD. Activation of these pathways degrades mHtt and other protein-containing polyQs, which restores proteostasis in these models. Hence, we propose 4QMn as a potential drug to develop a therapy to treat HD.

A novel amino-nanozyme, based on boehmite nanoparticles (BNPs) functionalised with a tetra-azapyridinophane (L1), has been designed to undermine some of the key issues underlying Huntington disease. L1 forms Cu 2+ complexes with a striking SOD activity, while when grafted to the BNPs displays mitoROS scavenging properties and ability to disaggregate mutant huntingtin deposits in cells.

NANOG is a key transcription factor required for maintaining pluripotency of embryonic stem cells. Elevated NANOG expression levels have been reported in many types of human cancers, including lung, oral, prostate, stomach, breast, and brain. Several studies reported the correlation between NANOG expression and tumor metastasis, revealing itself as a powerful biomarker of poor prognosis. However, how NANOG regulates tumor progression is still not known. We previously showed in medaka fish that Nanog regulates primordial germ cell migration through Cxcr4b, a chemokine receptor known for its ability to promote migration and metastasis in human cancers. Therefore, we investigated the role of human NANOG in CXCR4-mediated cancer cell migration. Of note, we found that NANOG regulatory elements in the CXCR4 promoter are functionally conserved in medaka fish and humans, suggesting an evolutionary conserved regulatory axis. Moreover, CXCR4 expression requires NANOG in human glioblastoma cells. In addition, transwell assays demonstrated that NANOG regulates cancer cell migration through the SDF1/CXCR4 pathway. Altogether, our results uncover NANOG-CXCR4 as a novel pathway controlling cellular migration and support Nanog as a potential therapeutic target in the treatment of Nanog-dependent tumor progression.

Continuous overexposure to sunlight increases its harmful effects on the skin. For this reason, there is a growing need to characterize economic models more representative of the negative effects and counteracting responses that irradiation causes on human skin. These models will serve for the screening of protective compounds against damage caused by ultraviolet (UV) and high energy visible light (HEV). Therefore, two common in vitro models employed for sunlight irradiation studies, namely human keratinocyte HaCat culture and reconstructed human epidermis (RHE), were compared with the medaka fish embryo model, traditionally used in other scientific disciplines. Using suberythemal doses of UVA and HEV to determine the level of Reactive Oxygen Species (ROS) generation and thymine dimers formed by UVB, we show that medaka embryo responds with a lower damage level, more comparable to human skin, than the other two models, probably due to the protective mechanisms that work in a complete organism. In the same way, the protective effects of antioxidant compounds have the greatest effect on medaka embryos. Taken together, these findings suggest that medaka embryos would be a good alternative in vitro model for sunlight effect studies, and for the screening of molecules with counteracting capacity against the damage caused by UV and HEV.

Oxidative stress (OS) can induce cell apoptosis and thus plays an important role in aging. Antioxidant foods protect tissues from OS and contribute to a healthier lifestyle. In this study, we described the used of medaka embryos (Oryzias latipes) to study the putative antioxidant capacity of dietary cocoa extract in vertebrates. A polyphenol-enriched cocoa extract regulated the expression of several genes implicated in OS, thereby protecting fish embryos from induced OS. The cocoa extract activated superoxide dismutase enzyme activity in embryos and adult fish tissues, suggesting a common mechanism for protection during embryonic development and adulthood. Furthermore, long-term feeding of the cocoa extract increased fish life span. Our study demonstrates that the polyphenol-enriched cocoa extract decreases OS and extends life span in medaka fish, validating the use of medaka embryos as an economical platform to screen the antioxidant capacity of food compounds.

Manganese complexes of polyamines consisting of an aza-pyridinophane macrocyclic core functionalised with side chains containing quinoline or pyridine units have been characterised by a variety of solution techniques and single crystal x-ray diffraction. Some of these compounds have proved to display interesting antioxidant capabilities in vitro and in vivo in prokaryotic (bacteria) and eukaryotic (yeast and fish embryo) organisms. In particular, the Mn complex of the ligand containing a 4-quinoline group in its side arm which, as it happens in the MnSOD enzymes, has a water molecule coordinated to the metal ion that shows the lowest toxicity and highest functional efficiency both in vitro and in vivo., (Copyright © 2014 Elsevier Inc. All rights reserved.)

To understand the molecular mechanisms that regulate the biology of embryonic stem cells (ESCs) it is necessary to study how they behave in vivo in their natural environment. It is particularly important to study the roles and interactions of the different proteins involved in pluripotency and to use this knowledge for therapeutic purposes. The recent description of key pluripotency factors like Oct4 and Nanog in non-mammalian species has introduced other animal models, such as chicken, Xenopus, zebrafish and medaka, to the study of pluripotency in vivo. These animal models complement the mouse model and have provided new insights into the evolution of Oct4 and Nanog and their different functions during embryonic development. Furthermore, other pluripotency factors previously identified in teleost fish such as Klf4, STAT3, Sox2, telomerase and Tcf3 can now be studied in the context of a functional pluripotency network. The many experimental advantages of fish will fuel rapid analysis of the roles of pluripotency factors in fish embryonic development and the identification of new molecules and mechanisms governing pluripotency.

Gonadal development in vertebrates depends on the early determination of primordial germ cells (PGCs) and their correct migration to the sites where the gonads develop. Several genes have been implicated in PGC specification and migration in vertebrates. Additionally, some of the genes associated with pluripotency, such as Oct4 and Nanog, are expressed in PGCs and gonads, suggesting a role for these genes in maintaining pluripotency of the germ lineage, which may be considered the only cell type that perpetually maintains stemness properties. Here, we report that medaka Nanog (Ol-Nanog) is expressed in the developing PGCs. Depletion of Ol-Nanog protein causes aberrant migration of PGCs and inhibits expression of Cxcr4b in PGCs, where it normally serves as the receptor of Sdf1a to guide PGC migration. Moreover, chromatin immunoprecipitation analysis demonstrates that Ol-Nanog protein binds to the promoter region of Cxcr4b, suggesting a direct regulation of Cxcr4b by Ol-Nanog. Simultaneous overexpression of Cxcr4b mRNA and depletion of Ol-Nanog protein in PGCs rescues the migration defective phenotype induced by a loss of Ol-Nanog, whereas overexpression of Sdf1a, the ligand for Cxcr4b, does not restore proper PGC migration. These results indicate that Ol-Nanog mediates PGC migration by regulating Cxcr4b expression.

We report the first case in the literature of Kyrieleis' vasculitis related to acute retinal necrosis by Varicella zoster virus in a 76-year-old woman with bilateral involvement. In our patient the arterial lesions appeared 15 days after the initial presentation.

Oct4 is a crucial transcription factor for controlling pluripotency in embryonic stem cells and the epiblast of mouse embryos. We have characterized the expression pattern of medaka (Oryzias latipes) Ol-Oct4 during embryonic development and in the adult gonads. Genomic analysis showed that Ol-Oct4 is the ortholog of zebrafish spg/pou2. However, their expression patterns are not the same, suggesting that Oct4 may play different roles in zebrafish and medaka. Using specific antibodies for the Ol-Oct4 protein, we showed that Ol-Oct4 is also expressed in primordial germ cells, in the spermatogonia (male germ stem cells), and during different stages of oocyte development. These results suggest that Ol-Oct4 plays a post-embryonic role in the maturing gonads and gametes. The Ol-Oct4 mRNA and protein expression patterns are similar to those of mammalian Oct4 and introduce medaka fish as a valid model for the functional and evolutionary study of pluripotency genes in vivo.

Differentiation of neural retinal precursor (NRP) cells in vertebrates follows an established order of cell-fate determination associated with exit from the cell cycle. Wnt signaling regulates cell cycle in colon carcinoma cells and has been implicated in different aspects of retinal development in various species. To better understand the biological roles of Wnt in the developing retina, we have used a transgenic and pharmacological approach to manipulate the Wnt signaling pathway during retinal development in medaka embryos. With the use of both approaches, we observed that during the early phase of retinal development Wnt signaling regulated cell cycle progression, proliferation, apoptosis, and differentiation of NRP cells. However, during later phases of retinal development, proliferation and apoptosis were not affected by manipulation of Wnt signaling. Instead, Wnt regulated Vsx1 expression, but not the expression of other retinal cell markers tested. Thus, the response of NRP cells to Wnt signaling is stage-dependent., ((c) 2009 Wiley-Liss, Inc.)

Nanog is involved in controlling pluripotency and differentiation of stem cells in vitro. However, its function in vivo has been studied only in mouse embryos and various reports suggest that Nanog may not be required for the regulation of differentiation. To better understand endogenous Nanog function, more animal models should be introduced to complement the murine model. Here, we have identified the homolog of the mammalian Nanog gene in teleost fish and describe the endogenous expression of Ol-Nanog mRNA and protein during medaka (Oryzias latipes) embryonic development and in the adult gonads. Using medaka fish as a vertebrate model to study Nanog function, we demonstrate that Ol-Nanog is necessary for S-phase transition and proliferation in the developing embryo. Moreover, inhibition or overexpression of Ol-Nanog does not affect gene expression of various pluripotency and differentiation markers, suggesting that this transcription factor may not play a direct role in embryonic germ layer differentiation. STEM CELLS 2009;27:2081-2091.

Diminished Sonic Hedgehog (Shh) signaling is associated with the most common forebrain defect in humans, holoprosencephaly (HPE), which includes cyclopia, a phenotype also seen in mice and other vertebrates with defective Shh signaling. The secreted protein Shh acts as a crucial factor that patterns the ventral forebrain and is required for the division of the primordial eye field and brain into two discrete halves. Gli2 is one of three vertebrate transcription factors implicated as obligatory mediators of Shh signal transduction. Here, we show that loss-of-function mutations in the human GLI2 gene are associated with a distinctive phenotype (within the HPE spectrum) whose primary features include defective anterior pituitary formation and pan-hypopituitarism, with or without overt forebrain cleavage abnormalities, and HPE-like midfacial hypoplasia. We also demonstrate that these mutations lack GLI2 activity. We report on a functional association between GLI2 and human disease and highlight the role of GLI2 in human head development.

Signaling pathways that play a fundamental role during development are turning out to underlie many disease states when misregulated. Here, we review some of the recent findings in the Hedgehog (Hh) pathway and the role it plays in different human diseases. We present a summary of the diseases that result from the inactivation or inappropriate activation of the Hh pathway. The human phenotypes generally fit the findings in model organisms and help to identify some potential targets for therapy.

Embryonic development in a given species is orchestrated by genes regulating growth and differentiation in a stereotyped and conserved manner, resulting in embryos of consistent size and shape. Several signaling pathways, including that of Sonic Hedgehog (SHH), have been implicated in these processes. Recent experiments with Gas1 indicate that it may act as a growth-inducing gene, challenging its previous function as a gene specifically involved in growth arrest. Moreover, GAS1, a GPI-linked membrane protein, can bind SHH, suggesting an interacting link between growth and patterning through SHH and GAS1.

There is growing evidence that Gli proteins participate in the mediation of Hedgehog and FGF signaling in neural and mesodermal development. However, little is known about which genes act downstream of Gli proteins. Here we show the regulation of members of the Wnt family by Gli proteins in different contexts. Our findings indicate that Gli2 regulates Wnt8 expression in the ventral marginal zone of the early frog embryo: activating Gli2 constructs induce ectopic Wnt8 expression in animal cap explants, whereas repressor forms inhibit its endogenous expression in the marginal zone. Using truncated Frizzled and dominant-negative Wnt constructs, we then show the requirement of at least two Wnt proteins, Wnt8 and Wnt11, for Gli2/3-induced posterior mesodermal development. Blocking Wnt signals, however, inhibits Gli2/3-induced morphogenesis, but not mesodermal specification. Gli2/3 may therefore normally coordinate the action of these two Wnt proteins, which regulate distinct downstream pathways. In addition, the finding that Gli1 consistently induces a distinct set of Wnt genes in animal cap explants and in skin tumors suggests that Wnt regulation by Gli proteins is general. Such a mechanism may link signals that induce Gli activity, such as FGFs and Hedgehogs, with Wnt function.

The Hedgehog (Hh) signal has an inductive role during Drosophila development. Patched is part of the Hedgehog-receptor complex and shows a repressive function on the signaling cascade, which is alleviated in the presence of Hh. Herein, we identify the first dominant gain-of-function allele of patched, Confused (patched(Con)). Analysis of the patched(Con) allele led us to uncover novel features of the reception and function of the Hh signal. At least three different regions of gene expression were identified and a gradient of cell affinities was established in response to Hh. A new state of Cubitus interruptus activity responsible for the activation of araucan and caupolican genes of the iroquois complex, independent of Fused kinase function, was shown. In the disc, patched(Con) behaved like fused mutants and was rescued by Suppressor of fused mutations. However, fused mutants are embryonic lethal while patched(Con) is not, suggesting that Patched could interpret Hedgehog signaling differently in the embryo and in the adult., (Copyright 2000 Academic Press.)

Patterning along the anteroposterior (A-P) axis involves the interplay of secreted and transcription factors that specify cell fates in the mesoderm and neuroectoderm. While FGF and homeodomain proteins have been shown to play different roles in posterior specification, the network coordinating their effects remains elusive. Here we have analyzed the function of Gli zinc-finger proteins in mesodermal A-P patterning. We find that Gli2 is sufficient to induce ventroposterior development, functioning in the FGF-brachyury regulatory loop. Gli2 directly induces brachyury, a gene required and sufficient for mesodermal development, and Gli2 is in turn induced by FGF signaling. Moreover, the homeobox gene Xhox3, a critical determinant of posterior development, is also directly regulated by Gli2. Gli3, but not Gli1, has an activity similar to that of Gli2 and is expressed in ventroposterior mesoderm after Gli2. These findings uncover a novel function of Gli proteins, previously only known to mediate hedgehog signals, in the maintenance and patterning of the embryonic mesoderm. More generally, our results suggest a molecular basis for an integration of FGF and hedgehog inputs in Gli-expressing cells that respond to these signals.

In the Drosophila wing imaginal disc, the Hedgehog (Hh) signal molecule induces the expression of decapentaplegic (dpp) in a band of cells abutting the anteroposterior (A/P) compartment border. It has been proposed that Dpp organizes the patterning of the entire wing disc. We have tested this proposal by studying the response to distinct levels of ectopic expression of Hh and Dpp, using the sensory organ precursors (SOPs) of the wing and notum and the presumptive wing veins as positional markers. Here, we show that Dpp specifies the position of most SOPs in the notum and of some of them in the wing. Close to the A/P compartment border, however, SOPs are specified by Hh rather than by Dpp alone. We also show that late signaling by Hh, after setting up dpp expression, is responsible for the formation of vein 3 and the scutellar region, and also for the determination of the distance between veins 3 and 4. One of the genes that mediates the Hh signal is the zinc-finger protein Cubitus interruptus (Ci). These results indicate that Hh has a Dpp-independent morphogenetic effect in the region of the wing disc near the A/P border.

The adult Drosophila wing (as the other appendages) is subdivided into anterior and posterior compartments that exhibit characteristic patterns. The engrailed (en) gene has been proposed to be paramount in the specification of the posterior compartment identity. Here, we explore the adult en function by targeting its expression in different regions of the wing disc. In the anterior compartment, ectopic en expression gives rise to the substitution of anterior structures by posterior ones, thus demonstrating its role in specification of posterior patterns. The en-expressing cells in the anterior compartment also induce high levels of the hedgehog (hh) and decapentaplegic (dpp) gene products, which results in local duplications of anterior patterns. Besides, hh is able to activate en and the engrailed-related gene invected (inv) in this compartment. In the posterior compartment we find that elevated levels of en product result in partial inactivation of the endogenous en and inv genes, indicating the existence of a negative autoregulatory mechanism. We propose that en has a dual role: a general one for patterning of the appendage, achieved through the activation of secreted proteins like hh and dpp, and a more specific one, determining posterior identity, in which the inv gene may be implicated.

The tom transposable element of Drosophila ananassae is mobilized with high frequency in the germ line of females from the ca; px strain, and its insertion results in mutations that show almost exclusively dominant eye phenotypes. tom is a long terminal repeat-containing retrotransposon that encodes three different open reading frames (ORFs). It is expressed in the nurse cells during oogenesis, in the central and peripheral nervous systems during embryonic development, and in the imaginal discs of the larva. tom RNA accumulates in the germarium of ovaries from ca; px females but not in the parental inactive strain, suggesting that this altered pattern of tom expression might be the cause of the high rate of mobilization of this retrotransposon. The specificity of tom-induced eye phenotypes can be explained by the presence of regulatory sequences responsible for expression of tom in the eye imaginal discs of third-instar larvae. These sequences might cause overexpression of adjacent genes affected by tom-induced mutations, resulting in the death of undifferentiated cells located anterior to the morphogenetic furrow. In addition to the full-length RNA, tom is also transcribed into a spliced subgenomic transcript that encodes a protein resulting from the fusion between the amino-terminal region of the first (gag) and the third ORFs. The protein encoded by this RNA shows structural characteristics such as a signal peptide, glycosylation sites, endopeptidase cleavage site, and fusion peptide that are typical of the envelope proteins of retroviruses. Antibodies against tom ORF3 recognize two different proteins present in female ovaries, suggesting that tom might be able to form infective viral particles that could play a role in the horizontal transmission of this retrotransposon.