Biomedical subjects

S Y Yu

Publications and source records attributed to S Y Yu.

At least 19 recordsLinked to original sources

PubMed2000

Mutation analysis of the putative tumor suppressor gene PTEN/MMAC1 in hepatocellular carcinoma.

Loss of heterozygosity of chromosome 10q has been reported in hepatoma. Areas with a high rate of loss of genetic material could harbor putative tumor suppressor genes. PTEN/MMAC1, a candidate tumor suppressor gene located at chromosome 10q23.3, has recently been identified and found to be homozygously deleted or mutated in several different types of human tumors. To determine whether the PTEN/MMAC1 gene is a target of 10q loss of heterozygosity in hepatoma, we examined 42 primary hepatomas for mutations in PTEN/MMAC1 by using nested reverse transcriptase polymerase chain reaction (RT-PCR) of the RNA and single-stranded conformation polymorphism (SSCP) analysis of all genomic exons. Although 2 of 42 hepatoma tissues had aberrant transcripts, 5 matched noncancerous liver tissues also had aberrant transcripts. Southern blot analysis of the entire genomic DNA revealed no genomic change. Therefore, like the TSG101 or FHIT gene, aberrant transcripts of PTEN/MMAC1 using the nested RT-PCR method were a common phenomenon for both cancerous and noncancerous liver tissues, which may not be related to oncogenesis. None of the 42 cases had small deletions, point mutations, or insertions. Our results suggest that the PTEN/MMAC1 gene may not play a role in the pathogenesis of hepatoma.

Blotting, Southern↗

PubMed2000

Establishment and characterization of a cell line (HCDB-1) derived from a hamster buccal pouch carcinoma induced by DMBA and Taiwanese betel quid extract.

This study identified that the carcinogenesis of hamster buccal pouch (HBP) induced by 7,12-dimethylbenz[a]anthracene (DMBA) was greatly enhanced (18 folds) by a combination treatment with Taiwanese betel quid (BQ) extract. A new cell line, HCDB-1, has been established from induced carcinomas. The cultured monolayer cells were epithelioid in shape with irregular nuclei. They demonstrated abundant cytokeratin and tonofilaments; however, ultrastructural well-organized desmosomes were lacking. The HCDB-1 cell exhibited population doubling in 19 h and was highly tumorigenic in nude mice. A C-->T transition at codon 141 (Ala to Val) of the p53 gene was detected in this cell. This mutation is equivalent to a specific temperature-sensitive mouse p53Ala135Val mutant that causes transformation by shifting to 37.5 degrees C. HCDB-1 is the first cell line established from the HBP model of oral carcinogenesis induced by DMBA/Taiwanese BQ extract. It might be valuable for exploring the molecular pathogenesis of oral cancer.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1999

Several levels of EGF receptor signaling during photoreceptor specification in wild-type, Ellipse, and null mutant Drosophila.

Dominant Ellipse mutant alleles of the Drosophila EGF receptor homologue (DER) dramatically suppress ommatidium development in the eye and induce ectopic vein development in the wing. Their phenotype suggests a possible role for DER in specifying the founder R8 photoreceptor cells for each ommatidium. Here we analyze the basis of Ellipse mutations and use them to probe the role of DER in eye development. We show that Elp mutations result from a single amino acid substitution in the kinase domain which activates tyrosine kinase activity and MAP kinase activation in tissue culture cells. Transformant studies confirmed that the mutation is hypermorphic in vivo, but the DER function was elevated less than by ectopic expression of the ligand spitz. Ectopic spi promoted photoreceptor differentiation, even in the absence of R8 cells. Pathways downstream of DER activation were assessed to explore the basis of these distinct outcomes. Elp mutations caused overexpression of the Notch target gene E(spl) mdelta and required function of Notch to suppress ommatidium formation. The Elp phenotype also depended on the secreted protein argos and was reverted in Elp aos double mutants. Complete loss of DER function in clones of null mutant cells led to delay in R8 specification and subsequently to loss of mutant cells. The DER null phenotype was distinct from that of either spitz or vein mutants, suggesting that a combination of these or other ligands was required for aspects of DER function. In normal development DER protein was expressed in most retinal cells, but at distinct levels. We used an antibody specific for diphospho-ERK as well as expression of the DER target gene argos to assess the pattern of DER activity, finding highest activity in the intermediate groups of cells in the morphogenetic furrow. However, studies of mutant genotypes suggested that this activity may not be required for normal ommatidium development. Since we saw distinct phenotypic effects of four different levels of DER activity associated with wild-type, null mutant, Elp mutant, or fully activated DER function, we propose that multiple thresholds separate several aspects of DER function. These include activation of N signaling to repress R8 specification, turning on argos expression, and recruiting photoreceptors R1-R7. It is possible that during normal eye development these thresholds are attained by different cells, contributing to the pattern of retinal differentiation.

Amino Acid Sequence↗

PubMed1999

Mutation analysis of the putative tumor suppression gene PTEN/MMAC1 in sporadic breast cancer.

PTEN/MMAC1, a potential human tumor suppressor gene, has been found to have inactivating mutations in several types of cancer, including breast cancer. The incidence of breast cancer in Chinese is quite low in comparison with Caucasians, and genetic factors may play some roles. To further determine the role of PTEN/MMAC1 in breast cancer in Chinese, we used loss of heterozygosity (LOH), single strand conformation polymorphism (SSCP) with direct sequencing of variant bands, and Southern blot analysis methods to analyze mutations in PTEN/MMAC1 in 52 cases of breast cancer. None had LOH at chromosome 10q23.3. One mutation was identified, a somatic 3-base deletion, in one case. Our results suggest PTEN/MMAC1 does not play a major role in the development of sporadic breast cancer.

Adult↗

PubMed1999

The effects of antagonizing residual neuromuscular blockade by neostigmine and glycopyrrolate on nausea and vomiting after ambulatory surgery.

UNLABELLED: The effects of neostigmine on the incidence of postoperative nausea and vomiting (PONV) are controversial. In this study, we evaluated the effects of neostigmine and glycopyrrolate on the incidence of PONV and the need for antiemetics in patients undergoing ambulatory surgery. One hundred healthy patients undergoing outpatient surgical procedures were included in the study. A standardized anesthetic technique was used for all patients. Patients were randomized to receive either mivacurium (n = 50) or rocuronium (n = 50) to achieve muscle paralysis. Bolus doses of mivacurium 2-4 mg or rocuronium 5-10 mg were administered to maintain one or two twitches of the train-of-four stimulation of the ulnar nerve at the wrist. After surgery, residual neuromuscular blockade was reversed with neostigmine 2.5 mg i.v. and glycopyrrolate 0.5 mg i.v. only if clinically deemed necessary (i.e., fade on train-of-four stimulation, inadequate tidal volume, reduced hand grip, or inability to maintain head lift). The incidence of PONV and the need for antiemetics were recorded in the post-anesthesia care unit (PACU), in the phase II unit, and 24 h after surgery. We compared patients who received neostigmine (n = 40) for reversal of residual neuromuscular blockade with those who did not (n = 60). More patients receiving rocuronium required reversal drugs than those receiving mivacurium (68% vs 10%). There were no differences in the incidence of nausea (18% vs 15%), vomiting (8% vs 12%), and the need for antiemetics (13% in both the groups) in the PACU between patients who received neostigmine and those who did not. In addition, the duration of PACU stay and the time to home-readiness were also similar between the groups. We conclude that, compared with rocuronium, the use of mivacurium decreases the need for reversal drugs. In addition, reversal of residual neuromuscular blockade with neostigmine does not increase the incidence of PONV or the need for antiemetic medications in patients undergoing ambulatory surgery. IMPLICATIONS: In this study, we showed that the incidence of postoperative nausea and vomiting and the need for antiemetics do not increase with the use of neostigmine and glycopyrrolate for reversal of residual muscle paralysis.

Adult↗

PubMed1999

CT features of systemic lupus erythematosus in patients with acute abdominal pain: emphasis on ischemic bowel disease.

PURPOSE: To evaluate the computed tomographic (CT) features of systemic lupus erythematosus (SLE) in patients with acute abdominal pain. Special emphasis was placed on the analysis of ischemic bowel disease. MATERIALS AND METHODS: The authors retrospectively reviewed the images from 39 abdominal CT examinations performed in 33 patients with SLE and acute abdominal pain. Images were evaluated for bowel wall changes, mesenteric changes, fluid collection, retroperitoneal lymphadenopathy, peritoneal enhancement, and hepatomegaly as well as for changes in other abdominal organs. Ischemic bowel disease was diagnosed if at least three of the following signs were seen: bowel wall thickening, target sign, dilatation of intestinal segments, engorgement of mesenteric vessels, and increased attenuation of mesenteric fat. RESULTS: Thirty-one (79%) of the 39 examinations had CT findings diagnostic of ischemic bowel disease, including symmetric bowel wall thickening (n = 29), target sign (n = 26), and mesenteric vascular engorgement and haziness (n = 31). In 24 cases, bowel wall thickening was multifocal, with variable length, and did not appear to be confined to a single vascular territory. CONCLUSION: The most common CT finding in patients with SLE and acute abdominal pain is ischemic bowel disease. CT is useful for detecting the primary cause of gastrointestinal symptoms, planning treatment, and monitoring for infarction or perforation.

Abdomen, Acute↗

PubMed1998

The R8-photoreceptor equivalence group in Drosophila: fate choice precedes regulated Delta transcription and is independent of Notch gene dose.

It has been suggested that lateral specification of cell fate by Notch signaling depends on feedback on Notch (N) and Delta (Dl) transcription to establish reciprocal distributions of the receptor and its ligand at the protein level. In Drosophila neurogenesis the predicted reciprocal protein distributions have not been observed. Either this model of lateral specification or the description of N and/or Dl protein distributions must be incomplete. We have reexamined R8 photoreceptor specification in the developing eye to resolve this question for this example of lateral specification. N and Dl protein levels were assessed in the cell as a whole and at the cell surface, where these proteins were mostly found at the intercellular cell junctions. Protein levels did not correspond to Notch signaling in wild type. However, Dl transcription and protein levels did correlate with altered N signaling in mutant genotypes. Our findings suggest the difference relates to the speed of lateral specification in vivo. The time required for N signaling to inhibit ato expression was at most 90 min, but changes in the Dl protein distribution in mutant genotypes arose more slowly. N expression was little regulated by N signaling, but protein encoded by the Nts1 allele was temperature-sensitive for appearance at the cell surface. Some aspects of the pattern of Dl protein appeared to be due to endocytosis. We conclude that feedback of N signaling on Dl transcription does occur but is too slow to account for the pattern of R8 specification. Studies of ommatidia mosaic for a Notch duplication, or for the Nts1 allele at semi-restrictive temperatures, found that cells beginning with less N activity were not necessarily predisposed to be selected for R8 differentiation. Our data argue that other signals may be responsible for the pattern of R8 cell fate allocation by N. Potential relevance to other neurogenic regions is discussed.

Animals↗

PubMed1998

Functional analysis of the fibrinogen-related scabrous gene from Drosophila melanogaster identifies potential effector and stimulatory protein domains.

The scabrous (sca) gene encodes a secreted dimeric glycoprotein with putative coiled-coil domains N-terminally and a C-terminal region related to the blood clot protein fibrinogen. Homozygous sca mutants have extra bristle organs and rough eyes. We describe a GAL4-based expression system for testing rescue of the sca mutant phenotype by altered SCA proteins and for misexpression. We find that deletion of the fibrinogen-related domain (FReD) greatly decreases SCA function, confirming the importance of this conserved region. SCA function could not be restored by FReDs from human fibrinogen chain genes. However, proteins lacking any FReD still showed some function in both rescue and misexpression experiments, suggesting that putative effector-binding regions lie outside this domain. Consistent with this, proteins expressing only the FReD had no rescuing activity but were recessive negative; i.e., they enhanced the phenotype of sca mutations but had no phenotype in the presence of a wild-type sca allele. This suggests that the FReD contributes to SCA function by binding to other components of the bristle determination pathway, increasing the activity of the linked N-terminal region.

Amino Acid Sequence↗

PubMed1998

Antiemetic activity of propofol after sevoflurane and desflurane anesthesia for outpatient laparoscopic cholecystectomy.

BACKGROUND: Controversy exists regarding the effectiveness of propofol to prevent postoperative nausea and vomiting. This prospective, randomized, single-blinded study was designed to evaluate the antiemetic effectiveness of 0.5 mg/kg propofol when administered intravenously after sevoflurane- compared with desflurane-based anesthesia. METHODS: Two hundred fifty female outpatients undergoing laparoscopic cholecystectomy were assigned randomly to one of four treatment groups. All patients were induced with intravenous doses of 2 mg midazolam, 2 microg/kg fentanyl, and 2 mg/kg propofol and maintained with either 1-4% sevoflurane (groups 1 and 2) or 2-8% desflurane (groups 3 and 4) in combination with 65% nitrous oxide in oxygen. At skin closure, patients in groups 1 and 3 were administered 5 ml intravenous saline, and patients in groups 2 and 4 were administered 0.5 mg/kg propofol intravenously. Recovery times were recorded from discontinuation of anesthesia to awakening, orientation, and readiness to be released home. Postoperative nausea and vomiting and requests for antiemetic rescue medication were evaluated during the first 24 h after surgery. RESULTS: Propofol, in an intravenous dose of 0.5 mg/kg, administered at the end of a sevoflurane-nitrous oxide or desflurane-nitrous oxide anesthetic prolonged the times to awakening and orientation by 40-80% and 25-30%, respectively. In group 2 (compared with groups 1, 3, and 4), the incidences of emesis (22% compared with 47%, 53%, and 47%) and requests for antiemetic rescue medication (19% compared with 42%, 50%, and 47%) within the first 6 h after surgery were significantly lower, and the time to home-readiness was significantly shorter in duration (216 +/- 50 min vs. 249 +/- 49 min, 260 +/- 88 min, and 254 +/- 72 min, respectively). CONCLUSIONS: A subhypnotic intravenous dose of propofol (0.5 mg/kg) administered at the end of outpatient laparoscopic cholecystectomy procedures was more effective in preventing postoperative nausea and vomiting after a sevoflurane-based (compared with a desflurane-based) anesthetic.

Adult↗

PubMed1998

Mast cell collagenase correlates with regression of pulmonary vascular remodeling in the rat.

Pulmonary vascular remodeling, produced by cell hypertrophy and extracellular matrix protein synthesis in response to hemodynamic stress, regresses after reduction of blood pressure, possibly by proteolysis of structural proteins. To test this postulate, we assessed the breakdown of extracellular matrix proteins and expression of collagenase and elastase in pulmonary arteries of rats exposed to hypoxia (10% O2 for 10 d) followed by normoxia. During hypoxia, contents of collagen and elastin increased in pulmonary arteries and latent rat interstitial collagenase was expressed without increased collagenolytic activity or mRNA levels. At 3 days after normoxia, collagen and elastin contents decreased coincident with the new appearance of activated collagenase and transient increases in collagenolytic and elastolytic activities. The amount of immunoreactive collagenase, localized predominately in connective tissue-type mast cells, was increased in the adventitia and media of hypertensive vessels. We conclude that mast cells containing latent collagenase are recruited into the outer walls of pulmonary arteries during remodeling. It is possible that mast cell-derived collagenase contributes to collagen breakdown in pulmonary arteries during early recovery from hypoxia and plays a role in restoration of vascular architecture.

Animals↗

PubMed1998

A subset of notch functions during Drosophila eye development require Su(H) and the E(spl) gene complex.

The Notch signalling pathway is involved in many processes where cell fate is decided. Previous work showed that Notch is required at successive steps during R8 specification in the Drosophila eye. Initially, Notch enhances atonal expression and promotes atonal function. After atonal autoregulation has been established, Notch signalling represses atonal expression during lateral specification. In this paper we investigate which known components of the Notch pathway are involved in each signalling process. Using clonal analysis we show that a ligand of Notch, Delta, is required along with Notch for both proneural enhancement and lateral specification, while the downstream components Suppressor-of-Hairless and Enhancer-of-Split are involved only in lateral specification. Our data point to a distinct signal transduction pathway during proneural enhancement by Notch. Using misexpression experiments we also show that particular Enhancer-of-split bHLH genes can differ greatly in their contribution to lateral specification.

Animals↗

PubMed1998

Cell death and proliferation and its relation to collagen degradation in uterine involution of rat.

Collagen concentration, procollagenase localization, and their association with cell proliferation and apoptosis during postpartum involution, were investigated biochemically and histochemically in postpartum day 1, 3, 5, and 7 rat uterine tissues. In control animals, uterine wet weight, soluble protein, and collagen decreased rapidly during days 1 to 3 postpartum, and the DNA concentration in the uterine horn rapidly decreased, as noted by others. Simultaneously, both apoptosis and cell proliferation were observed in these tissues. These processes were highest in smooth muscle cells on day 3 postpartum. Procollagenase was found in the cell cytoplasm through days 1 to 3 postpartum, was highest on the third day postpartum, and appeared to gradually diminish by day 5 postpartum. Disorganization of collagen fibers was observed, under polarized microscopy by a strong birefringence of collagen fibers of the circular smooth muscle cell layers. However, this disorganization of the uterine collagen diminished progressively from day 3 to day 7. Treatment with estradiol or a combination of estradiol and progesterone suppressed cellular turnover and attenuated the changes in DNA, total amino acids, and collagen on day 3 postpartum. In this study, cellular turnover and biochemical and morphological changes appeared to be closely associated. Gonadal steroid hormones appear to influence these changes and retard uterine involution. This study suggests that a dynamic turnover of the cellular population takes place during uterine involution. It is possible that other factors, in addition to steroid hormones, contribute to uterine involution. It is to be postulated that these factors either are themselves decreased or, alternatively, may increase the inhibition of other unknown factors by an indirect mechanism.

Animals↗

PubMed1997

Proneural function of neurogenic genes in the developing Drosophila eye.

BACKGROUND: . Intercellular signals are major determinants of cell fate during development. Certain signals and receptors are important for many different cell-fate decisions, suggesting that cellular responses to similar signals change during development. Few transitions between such distinct cellular responses have been studied. The Drosophila genes Notch and hedgehog function during intracellular signaling at various stages of development. In the specific case of development of the Drosophila eye, expression of the proneural gene atonal is induced in response to Hedgehog signaling and then becomes subject to autoregulation. The receptor protein Notch has previously been reported to function in the selection of single founder photoreceptor cells (R8 cells) by inhibiting atonal expression. On this basis, complete elimination of Notch gene function would be expected to cause neural hyperplasia in the eye. RESULTS: . Contrary to expectation, we detect a reduction in neural differentiation both in cells expressing a conditional Notch allele and in those lacking expression of either Notch or its ligand Delta. We show here that Notch signaling acts after the initial Hedgehog-driven expression of atonal to enhance proneural competence of the atonal-expressing cells and also to terminate their response to the Hedgehog signals. This occurs before the Notch-induced lateral inhibition of atonal expression within the same cells. CONCLUSION: . Notch has sequentially opposite effects on the same cells, by first promoting and then inhibiting proneural gene function. This apparently paradoxical sequence of events has two possible consequences. Firstly, coupling of alternative cellular responses to the same receptor may prevent them from occurring simultaneously. Secondly, consecutive regulatory processes become temporally coupled, so that these events follow on from each other, without gaps or overlaps.

Animals↗

PubMed1997

Protective role of selenium against hepatitis B virus and primary liver cancer in Qidong.

High rates of hepatitis B virus (HBV) infection and primary liver cancer (PLC) are present in Qidong county. Epidemiological surveys demonstrated an inverse association between selenium (Se) level and regional cancer incidence, as well as HBV infection. Four-year animal studies showed that dietary supplement of Se reduced the HBV infection by 77.2% and liver precancerous lesion by 75.8% of ducks, caused by exposure to natural environmental etiologic factors. An intervention trial was undertaken among the general population of 130,471. Individuals in five townships were involved for observation of the preventive effect of Se. The 8-yr follow-up data showed reduced PLC incidence by 35.1% in selenized table salt supplemented vs the nonsupplemented population. On withdrawal of Se from the treated group, PLC incidence rate began to increase. However, the inhibitory response to HBV was sustained during the 3-yr cessation of treatment. The clinical study among 226 Hepatitis B Surface Antigen (HBsAg)-positive persons provided either 200 micrograms of Se in the form of selenized yeast tablet or an identical placebo of yeast tablet daily for 4 yr showed that 7 of 113 subjects were diagnosed as having PLC in the placebo group, whereas no incidence of PLC was found in 113 subjects supplemented with Se. Again on cessation of treatment, PLC developed at a rate comparable to that in the control group, demonstrating that a continuous intake of Se is essential to sustain the chemopreventive effect.

Adult↗

PubMed1997

Detection of elastin in the human fetal membranes: proposed molecular basis for elasticity.

The human fetal membranes provide a sterile biomechanical container which adjust by growth to mid-pregnancy to the increase in fetal size, and by elasticity to the forceful movements of the fetus. The molecular basis for this elasticity is not known, yet reduced elasticity may lead to their premature rupture and preterm birth, a major problem in perinatal medicine. Classically, elastin confers the property of elastic recoil to elastic fibres which are assembled from a family of tropoelastin precursors. These are covalently cross-linked to form insoluble elastin by formation of desmosine and isodesmosine, catalysed by the enzyme lysyl oxidase. The amnion, chorion and decidua were shown by Northern analysis and RT-PCR to contain detectable levels of tropoelastin mRNA and the mRNA encoding lysyl oxidase. The proteins encoded by these mRNAs were also identified by Western blotting and immunolocalization. Further, insoluble elastin was extracted from the human fetal membranes and shown by comparison to elastin preparations from other elastic tissues to have a reasonable desmosine content. Finally, scanning electron microscopy confirmed the presence of multiple layers of an apparently very thin elastic system in this tissue. This biochemical and histopathologic study has demonstrated therefore that the human fetal membranes synthesize and deposit a novel elastic fibre. The presence of such an elastic system in these tissues provides, for the first time, a probable molecular basis for the elastic properties of this tissue.

Amino Acids↗

PubMed1997

Diagnostic laparoscopy: indication and benefit.

BACKGROUND: Patients with an obscure and unrelievable abdominal condition may be forced to receive open laparotomy for diagnosis. Diagnostic laparoscopy has been suggested as an alternative to diagnostic laparotomy in selected cases. The aim of this article is to evaluate the circumstances suitable for laparoscopic diagnosis of certain abdominal conditions and the possible advantages of that approach. METHODS: Among 256 patients undergoing elective laparoscopic operations using conventionally pneumoperitoneal techniques from January 1994 to June 1995, twenty patients received diagnostic laparoscopy. The correlation between preoperative diagnosis, laparoscopic diagnosis and pathologic diagnosis as well as the outcome of laparoscopic diagnosis and treatment have been assessed. RESULTS: Major indications for diagnostic laparoscopy included acute abdominal pain (n = 4), chronic abdominal pain (n = 6), differentiating intraabdominal tumor (n = 4), staging known malignancy (n = 3) and evaluating intraperitoneal implantation (n = 3). Two of the four patients with acute abdominal conditions, one of the six patients with chronic abdominal pain. Four of the seven patients with undifferentiated/unstaged abdominal tumors and all of the three patients with intraperitoneal-implanted drainage tubes had no reasons for a further exploratory procedure, thus preventing the morbidity or mortality which might occur after unnecessary laparotomy. The duration of operation and hospitalization was shorter than the group without laparotomy. CONCLUSIONS: Diagnostic laparoscopy benefits patients by avoiding unnecessary surgery, avoiding unnecessary delay in diagnosis and treatment and shortening the operative and hospitalized period. However, it provides only an alternative not a substitute for traditional diagnostic procedures and will never lessen the importance of conventional laparotomy.

Abdomen, Acute↗

PubMed1996

Decreased endurance to cold water swimming and delayed sexual maturity in the rat following neonatal lead exposure.

The effects of neonatal lead (Pb) exposure on ability to endure stress and on the onset of sexual maturity were investigated using rats. Sprague-Dawley dams (n = 17/treatment) were treated with or without lead acetate (0.3%) in drinking water from parturition until postnatal day (PND) 21, at which time the pups were weaned. A set of sex-balanced pairs of pups (24 male and 24 females/treatment) from randomly selected control and Pb-treated dams was tested for cold water (4 degrees C) swimming-endurance on PND 15, 21, 25 and 30. Lead treated-female pups showed significantly (P < 0.05) lower endurance on PND 21 and 30, while Pb-treated males exhibited lower (P < 0.05) endurance on PND 21 compared to their respective controls. The results of this study indicate that neonatal exposure to Pb decreased cold water swimming-endurance. Neonatal exposure to either Pb or swimming stress delayed (P < 0.002) the onset of sexual maturity in both sexes. However, exposure to both treatments masked the effect of swimming stress on the onset of maturity in females but not in males.

Analysis of Variance↗

PubMed1996

The scabrous gene encodes a secreted glycoprotein dimer and regulates proneural development in Drosophila eyes.

R8 photoreceptor cells play a primary role in the differentiation of Drosophila eyes. In scabrous (sca) mutants, the pattern of R8 photoreceptor differentiation is altered. The sca gene is predicted to encode a secreted protein related in part to fibrinogen and tenascins. Using expression in Drosophila Schneider cells, we showed that sca encoded a dimeric glycoprotein which was secreted and found in soluble form in the tissue culture medium. The sca protein contained both N- and O-linked carbohydrates and interacted with heparin. This Schneider cell protein was similar to protein detected in embryos. We showed that sca mutations, along with conditional alleles of Notch (N) and Delta (Dl), each affected the pattern of cells expressing atonal (ato), the proneural gene required for R8 differentiation. In normal development, about 1 cell in 20 differentiates into an R8 cell; in the others, ato is repressed. N and Dl were required to repress ato in the vicinity of R8 cells, whereas sca had effects over several cell diameters. Certain antibodies detected uptake of sca protein several cells away from its source. The overall growth factor-like structure of sca protein, its solubility, and its range of effects in vivo are consistent with a diffusible role that complements mechanisms involving direct cell contact. We propose that as the morphogenic furrow advances, cell secreting sca protein control the pattern of the next ommatidial column.

Amino Acid Sequence↗