Effect of monochorionicity on perinatal outcome and growth discordance in triplet pregnancy: collaborative multicenter study in England, 2000-2013.

OBJECTIVES: To compare perinatal outcome and growth discordance between trichorionic triamniotic (TCTA) and dichorionic triamniotic (DCTA) or monochorionic triamniotic (MCTA) triplet pregnancies. METHODS: This was a multicenter cohort study using population-based data on triplet pregnancies from 11 Northern Survey of Twin and Multiple Pregnancy (NorSTAMP) maternity units and the Southwest Thames Region of London Obstetric Research Collaborative (STORK) multiple pregnancy cohort, for 2000-2013. Perinatal outcomes (from ≥ 24 weeks' gestation to 28 days of age), intertriplet fetal growth and birth-weight (BW) discordance and neonatal morbidity were analyzed in TCTA compared with DCTA/MCTA pregnancies. RESULTS: Monochorionic placentation of a pair or trio in triplet pregnancy (n = 72) was associated with a significantly increased risk of perinatal mortality (risk ratio, 2.7 (95% CI, 1.3-5.5)) compared with that in TCTA pregnancies (n = 68), due mainly to a much higher risk of stillbirth (risk ratio, 5.4 (95% CI, 1.6-18.2)), with 57% of all stillbirth cases resulting from fetofetal transfusion syndrome, while there was no significant difference in neonatal mortality (P = 0.60). The associations with perinatal mortality and stillbirth persisted when considering only pregnancies not affected by a major congenital anomaly. DCTA/MCTA triplets had lower BW and demonstrated greater BW discordance than did TCTA triplets (P = 0.049). Severe BW discordance of > 35% was 2.5-fold higher in DCTA/MCTA compared with TCTA pregnancies (26.1% vs 10.4%), but this difference did not reach statistical significance (P = 0.06), presumably due to low numbers. Triplets in both groups were delivered by Cesarean section in over 95% of cases, at a similar gestational age (median, 33 weeks' gestation). The rate of respiratory (P = 0.28) or infectious (P = 0.08) neonatal morbidity was similar between the groups. CONCLUSIONS: Despite close antenatal surveillance, monochorionic placentation of a pair or trio in triamniotic triplet pregnancy was associated with a significantly increased stillbirth risk, mainly due to fetofetal transfusion syndrome, and with greater size discordance. In liveborn triplets, there was no adverse effect of monochorionicity on neonatal outcome. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Prevalence, antenatal management and perinatal outcome of monochorionic monoamniotic twin pregnancy: a collaborative multicenter study in England, 2000-2013.

OBJECTIVES: To determine the prevalence of monochorionic monoamniotic (MCMA) twin pregnancy and to describe perinatal outcome and clinical management of these pregnancies. METHODS: In this multicenter cohort study, the prevalence of MCMA twinning was estimated using population-based data on MCMA twin pregnancies, collected between 2000 and 2013 from 11 Northern Survey of Twin and Multiple Pregnancy (NorSTAMP) maternity units. Pregnancy outcome at < 24 weeks' gestation, antenatal parameters and perinatal outcome (from ≥ 24 weeks to the first 28 days of age) were analyzed using combined data on pregnancies confirmed to be MCMA from NorSTAMP and the Southwest Thames Region of London Obstetric Research Collaborative (STORK) multiple pregnancy cohort for 2000-2013. RESULTS: The estimated total prevalence of MCMA twin pregnancies in the North of England region was 8.2 per 1000 twin pregnancies (59/7170), and the birth prevalence was 0.08 per 1000 pregnancies overall (singleton and multiple). Using combined data from NorSTAMP and STORK, the rate of fetal death (at < 24 weeks' gestation), including terminations of pregnancy and selective feticide, was 31.8% (54/170); the overall perinatal mortality rate was 14.7% (17/116), ranging from 69.2% at < 30 weeks to 4.5% at ≥ 33 weeks' gestation. MCMA twins that survived in utero beyond 24 weeks were delivered, usually by Cesarean section, at a median of 33 (interquartile range, 32-34) weeks of gestation. CONCLUSIONS: In MCMA twins surviving beyond 24 weeks of gestation, there was a higher survival rate compared with in previous decades, presumably due to early diagnosis, close surveillance and elective birth around 32-34 weeks of gestation. High perinatal mortality at early gestations was attributed mainly to extreme prematurity due to preterm spontaneous labor. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

The use of O-ring retractors at Caesarean section : A systematic review and meta analysis.

O-ring retractors (Alexis/Mobius) have been shown to reduce the risk of Surgical site infection (SSI) following general abdominal surgery. The benefit at caesarean section (CS) remains to be established given the relatively high cost. OBJECTIVES: To assess the efficacy of O-ring retractors when used at CS. STUDY DESIGN: Systematic review and meta-analysis. Electronic databases were searched from inception of each database until January 2018. No language restrictions were applied. All randomised controlled trials (RCTs) which compared the use of an O-ring retractor to routine care at CS were included. Primary outcome was SSI. Secondary outcomes were operating time, estimated blood loss, need for blood transfusion, need to exteriorise the uterus, requirement for additional postoperative analgesia and adequate operative field visualisation. Analysis was performed using Revman 5.3. RESULTS: 6 RCTs were included in the qualitative synthesis and the meta-analysis. This included 1669 women. The use of O-ring retractors did not reduce the risk of SSI when used at CS RR 0.76 (95% CI 0.34-1.70). Nor did the use of O-ring retractors reduce the operating time, estimated blood loss, the need for blood transfusion or the need for additional postoperative analgesia. The use O-ring retractors did reduce the need for exteriorisation of the uterus RR 0.48 (95% CI 0.33-0.69), and did increase the rate of adequate visualisation of the operative field RR 1.05 (95% CI 1.00-1.10). In a planned subgroup analysis there was a reduction in the rate of SSI with the use of O-ring retractors in women with a BMI < 35 RR 0.34(95% CI 0.12-0.98). CONCLUSION: This review has shown that O-ring retractors do not reduce the incidence of the common measurable complications of CS; SSI, blood loss, need for blood transfusion and need for additional postoperative analgesia. There may be a subgroup where these retractors are useful, but present evidence does not justify their routine use at CS.

Caesarean section at maternal request--the differing views of patients and healthcare professionals: a questionnaire based study.

OBJECTIVE: The number of caesarean sections at maternal request without medical indication is increasing. We aimed to explore the views of pregnant women, midwives and doctors using six hypothetical clinical scenarios and compare group views on: (a) perceived appropriateness of requests for caesarean section and (b) the reasons underlying these requests. STUDY DESIGN: A questionnaire was distributed to 166 pregnant women, 31 midwives and 52 doctors within maternity units at two hospitals in the North East region of England. Six hypothetical clinical scenarios for maternal requests were used: (1) uncomplicated first pregnancy, (2) one previous normal delivery, (3) one previous instrumental delivery, (4) one previous caesarean section, (5) one previous caesarean section with vaginal delivery since and (6) uncomplicated twin pregnancy. To highlight the differences in group responses, two main questions were asked for each scenario: 1. Should women be able to request a caesarean section? 2. What do you feel are the reasons for requesting a caesarean section? Data was analysed using Chi-squared or likelihood ratio as appropriate. RESULTS: In scenarios 1-3, professional groups were 'less likely' than pregnant women to always support a request (2.4% vs. 19.4%), (2.6% vs. 15.6%), (4.6% vs. 22%), (p<0.001). No significant differences were shown between doctors and midwives except for scenario 6 (twins), where midwives more often felt maternal requests should be declined (26.1% vs. 1.9%) (p=0.001). Multiparous women (n=95) were more likely to agree 'sometimes' to maternal requests in scenarios 1, compared to nulliparous women (n=71) (21.1% vs. 4.2%) (p=0.04). 'Safety of the baby' was ranked highly with pregnant women in scenarios 1-3 (mean 24.4%, range [15.8-38%]) compared with healthcare professionals (7.6% [3.4-12.8%]). However in scenario 3, healthcare professionals attributed 'fear of injury to self' (29.6%) as the most likely reason compared to 14.6% of pregnant women. CONCLUSION: Healthcare professionals and pregnant women's views differ significantly. Multiparous patients' views differ from those who have not had children before. We should provide clearer information on risks and benefits which encompass areas that concern women most.

Women's perception of future risk following pregnancies complicated by preeclampsia.

OBJECTIVE: To elicit women's personal understanding of future cardiovascular risk, following a pregnancy complicated by preeclampsia, and to identify the postnatal needs of these women. METHODS: Semi-structured interviews with 12 women with a recent history of preeclampsia who had attended a postnatal follow-up clinic. RESULTS: The interviews were held at a median of 47 weeks postpartum (range 24-62 weeks). Family history of cardiovascular disease was associated with a greater awareness of future cardiovascular risk. Women without traditional risk factors found it hard to envisage themselves as being at risk and may not see the relevance of such information. It may take several months after delivery for a woman to be able to fully consider her own health as well as the baby's; a reminder of risk and health information is needed. CONCLUSIONS: Although receptive to follow-up, the situational factors of being a new mother need to be taken into account to engage successfully with this patient group. Further research is needed to help clarify the extent to which a history of preeclampsia is an independent factor for future cardiovascular disease to provide a solid foundation for effective risk communication.

Drosophila vitelline membrane assembly: a critical role for an evolutionarily conserved cysteine in the "VM domain" of sV23.

The vitelline membrane (VM), the oocyte proximal layer of the Drosophila eggshell, contains four major proteins (VMPs) that possess a highly conserved "VM domain" which includes three precisely spaced, evolutionarily conserved, cysteines (CX7CX8C). Focusing on sV23, this study showed that the three cysteines are not functionally equivalent. While substitution mutations at the first (C123S) or third (C140S) cysteines were tolerated, females with a substitution at the second position (C131S) were sterile. Fractionation studies showed that sV23 incorporates into a large disulfide linked network well after its secretion ceases, suggesting that post-depositional mechanisms are in place to restrict disulfide bond formation until late oogenesis, when the oocyte no longer experiences large volume increases. Affinity chromatography utilizing histidine tagged sV23 alleles revealed small sV23 disulfide linked complexes during the early stages of eggshell formation that included other VMPs, namely sV17 and Vml. The early presence but late loss of these associations in an sV23 double cysteine mutant suggests that reorganization of disulfide bonds may underlie the regulated growth of disulfide linked networks in the vitelline membrane. Found within the context of a putative thioredoxin active site (CXXS) C131, the critical cysteine in sV23, may play an important enzymatic role in isomerizing intermolecular disulfide bonds during eggshell assembly.

The functions of the multiproduct and rapidly evolving dec-1 eggshell gene are conserved between evolutionarily distant species of Drosophila.

The Drosophila dec-1 gene encodes multiple proteins that are required for female fertility and proper eggshell morphogenesis. Genetic and immunolocalization data suggest that the different DEC-1 proteins are functionally distinct. To identify regions within the proteins with potential biological significance, we cloned and sequenced the D. yakuba and D. virilis dec-1 homologs. Interspecies comparisons of the predicted translation products revealed rapidly evolving sequences punctuated by blocks of conserved amino acids. Despite extensive amino acid variability, the proteins produced by the different dec-1 homologs were functionally interchangeable. The introduction of transgenes containing either the D. yakuba or the D. virilis dec-1 open reading frames into a D. melanogaster DEC-1 protein null mutant was sufficient to restore female fertility and wild-type eggshell morphology. Normal expression and extracellular processing of the DEC-1 proteins was correlated with the phenotypic rescue. The nature of the conserved features highlighted by the evolutionary comparison and the molecular resemblance of some of these features to those found in other extracellular proteins suggests functional correlates for some of the multiple DEC-1 derivatives.

Two-year outcomes of intrastromal corneal ring segments for the correction of myopia.

OBJECTIVE: To evaluate the safety and efficacy of Intrastromal Corneal Ring Segments (ICRS) for the correction of myopia. DESIGN: Nonrandomized, comparative trial. PARTICIPANTS: Patients enrolled in the United States Food and Drug Administration phase II and phase III clinical trials of the ICRS had best spectacle-corrected visual acuity (BSCVA) of 20/20 or better, myopia of -1.00 to -3.50 diopters (D), and a cylindrical correction of 1.00 D or less as measured by manifest refraction. INTERVENTION: Surgical correction of myopia with an ICRS. MAIN OUTCOME MEASURES: Efficacy was assessed by predictability of refractive outcome (deviation from predicted cycloplegic refraction spherical equivalent), stability of refractive effect, and postoperative uncorrected visual acuity. Safety was assessed by adverse events, maintenance or loss of preoperative BSCVA, and induced manifest refraction cylinder. RESULTS: Four hundred fifty-two patients were enrolled at 11 investigational sites in both studies. Of the 454 surgical attempts, 449 received an ICRS in one eye (0.25, 0.30, and 0.35 mm in 148, 151, and 150 eyes, respectively). First surgeries were attempted in 452 patients. An ICRS was successfully implanted in 447 initial eyes, and 5 surgeries were discontinued. Of the five discontinued surgeries, three patients subsequently exited from the study, and two patients went on to have the ICRS implanted in the second eye, bringing the total number of successful implants to 449 patient eyes. Month 24 postoperative follow-up was completed on 358 patients (80%). At month 24, 328 of 354 eyes (93%) were within +/-1.00 D of predicted refractive outcome. Refraction changed by 1 D or less in 97% of eyes (421/435) between 3 and 6 months after implantation and in 99% (343/348) between months 18 and 24. Before surgery, 87% of eyes (390/448) saw worse than 20/40 uncorrected; 24 months after surgery, 55% of eyes (196/358) saw 20/16 or better, 76% (271/358) saw 20/20 or better, and 97% (346/358) saw 20/40 or better. Although two eyes (2/358; 0.5%) lost two or more lines of BSCVA at 24 months; visual acuity in both was 20/20 or better. Intraoperative complications included anterior corneal surface perforation (three eyes) and anterior chamber perforations (two eyes, one during an attempted exchange procedure); all healed spontaneously without suturing and without loss of BSCVA. The ICRS was repositioned in five eyes to increase correction. Postoperative complications in one eye each were infectious keratitis, shallow segment placement, and loss of two lines of BSCVA at two or more consecutive examinations (subsequently regained). CONCLUSIONS: The ICRS safely, predictably, and effectively reduced or eliminated myopia of -1.00 to -3.50 D. The refractive effect was stable over time.

Laser in situ keratomileusis: surgical technique.

Laser in-situ keratomileusis is an increasingly popular technique for the correction of refractive errors that was initially described by Pallikaris in 1990. It involves the excimer laser ablation of corneal stroma beneath a hinged corneal flap that is created with a microkeratome. The purpose of this chapter is to report the LASIK surgical technique that has evolved at the Emory Vision Correction Center since 1995 when an investigation study of this technique for the correction of myopia began.

Differential sorting of constitutively co-secreted proteins in the ovarian follicle cells of Drosophila.

Conventional and freeze-fracture electron microscopy, immuno-electron microscopy of ovarian cryosections and confocal immunofluorescence were used to analyze the ovarian distribution of the major protein classes being secreted by the follicle cells during the vitellogenic and choriogenic stages of Drosophila oogenesis. Our results clearly demonstrated that at vitellogenic stages the follicle cells co-secrete constitutively vitelline membrane and yolk proteins that are either sorted into distinct secretory vesicles or they are segregated in different parts of bipartite vesicles by differential condensation. Following their exocytosis only the vitelline membrane proteins are incorporated into the forming vitelline membrane. The yolk proteins (along with their hemolymph circulating counterparts) diffuse through gaps amongst the incomplete vitelline membrane and are internalized through endocytosis by the oocyte where they are finally stored into modified lysosomes referred to as alpha-yolk granules. The unexpected immunolocalization of vitelline membrane antigens in the associated body of the alpha-yolk granules may indicate that this structure is a transient repository for the proteins being internalized into the oocyte along with the yolk proteins. In the early choriogenic follicle cells the vitelline membrane and early chorion proteins were found to be co-secreted and to be evenly intermixed into the same secretory vesicles. These findings illuminate new details concerning the follicle cells secretory and oocyte endocytic pathways and provide for the first time evidence for condensation-mediated sorting of constitutively secreted proteins in Drosophila.

Intrastomal corneal ring segments: reversibility of refractive effect.

PURPOSE: To evaluate the reversibility of refractive effect following removal of the ICRS (intrastromal corneal ring segments; Intacs). METHODS: Data from 34 eyes from which ICRS were removed during United States FDA Phase II and III clinical trials were evaluated with regard to segment size, loss or change of best spectacle-corrected visual acuity (BSCVA), any change of uncorrected visual acuity (UCVA), manifest spherical equivalent refraction, manifest cylinder refraction, stability of manifest cylinder refraction, and subjective visual symptoms. RESULTS: Out of 725 initial or contralateral eyes placed with the ICRS during Phase II and III clinical trials, segments were removed from 34 eyes (4.7%). Other than one (1/725, 0.1%) safety related ICRS removal, 30/725 (4.1%) were due to visual symptoms. ICRS removal was accomplished under topical anesthesia without complications in all eyes. The mean length of time the segments remained in the cornea after initial surgery was 10.3 +/- 5.4 months. At 3 months after ICRS removal, 21 eyes had monitored data available and were within +/-1 line or 10 letters of their preoperative BSCVA. Twenty eyes (20/21, 95%) returned to within +/-1.00 D of their preoperative manifest spherical equivalent refraction. All eyes had a stable refraction at the 3-month examination after removal, and a manifest spherical equivalent refraction within +/-1.00 D of their 1-month examination after removal. Nineteen eyes (19/21, 90%) returned to within +/-2 lines and 16 eyes (16/21, 76%) returned to within +/-1 line of preoperative UCVA. CONCLUSION: The ICRS (Intacs) was easily and safely removed, and eyes returned to preoperative refractive status within 3 months.

Effects of laser in situ keratomileusis (LASIK) on the corneal endothelium 3 years postoperatively.

PURPOSE: To investigate the effects of laser in situ keratomileusis (LASIK) on the corneal endothelium 3 years postoperatively. METHODS: Patients who were subjects of a previous prospective study (Am J Ophthalmol 125:465-471, (April) 1998) were contacted for a follow-up analysis of the central corneal endothelium. Noncontact specular microscopy was performed 35 to 37 months after LASIK on 52 eyes of 27 patients of the original cohort of 98 eyes of 65 patients and six eyes of three patients who were previously lost to follow-up after their initial post-LASIK evaluation. Patient age ranged from 29 to 66 years at the time of the original LASIK procedure. Attempted corrections ranged from 2.25 to 14.5 diopters of myopia, giving theoretical ablation depths of 182 to 332 microm below the corneal surface. Forty-eight eyes (83%) had a history of preoperative contact lens use (3 to 33 years). Central endothelial cell density, coefficient of variation of cell size, and percent of hexagonal cells were analyzed using 72 to 152 cells from each image. Multivariate analysis was used to search for factors that might predict changes in cell density, coefficient of variation, and percent of hexagonal cells. RESULTS: The mean +/- SD preoperative cell density was 2,498 +/- 354 cells per mm(2), the mean coefficient of variation was 0.36 +/- 0.07, and the percent of hexagonal cells was 58 +/- 6. Three years after surgery there was no statistically significant change in the mean endothelial cell density (2,489 +/- 335 cells per mm(2); P = 0.88, paired t test) or the percent of hexagonal cells (60 +/- 7; P = 0.14, paired t test). The mean coefficient of variation was significantly lower postoperatively (0.32 +/- 0.04; P = 0.0006, paired t test); a repeated measures analysis showed that this significant improvement could not be explained by cessation of contact lens wear after LASIK (P = 0.34). Multivariate analysis did not identify any factors that were predictive of change in cell density, coefficient of variation, and percent of hexagonal cells. CONCLUSIONS: Laser in situ keratomileusis for the correction of 2.25 to 14.5 diopters of myopia had no significant effect on central corneal endothelial cell density or the percent of hexagonal cells 3 years after surgery. The coefficient of variation of cell size improved significantly 3 years after surgery.

Laser in situ keratomileusis for myopia up to -11 diopters with up to -5 diopters of astigmatism with the summit autonomous LADARVision excimer laser system.

OBJECTIVE: To assess the safety and effectiveness of the Summit Autonomous LADARVision active tracking narrow beam excimer laser system for laser in situ keratomileusis (LASIK) correction of myopia and astigmatism. DESIGN: A multicenter, prospective noncomparative case series. PARTICIPANTS: This cohort consisted of 177 eyes corrected for spherical myopia up to -11 diopters (D) and 170 eyes corrected for myopia up to -11 D spherical equivalent with astigmatism up to -5 D. INTERVENTION: Treatments were performed at four sites in the United States using a 6-mm optic zone for spherical myopes and a 5.5-mm optic zone with a 1-mm blend for astigmats. MAIN OUTCOME MEASURES: Visual acuity, subjective refraction, vector analysis, subject satisfaction, intraocular pressure, complications, and adverse reactions. RESULTS: Six-month follow-up was available on 157 spherical eyes and 113 astigmatic eyes. For spherical myopes, uncorrected visual acuity (UCVA) was 20/20 or better in 60.5%, 20/25 or better in 80.3%, and 20/40 or better in 93.9%. The mean spherical equivalent was -0.29 +/- 0.45 D with 75.2% +/- 0.50 D and 94.9% +/- 1.00 D of intended. A loss of two lines of best spectacle-corrected visual acuity (BSCVA) occurred in 0.6%, and no eyes lost greater than two lines of BSCVA. For astigmatic myopes, UCVA was 20/20 or better in 52.0%, 20/25 or better in 74.5%, and 20/40 or better in 94.1%. The mean spherical equivalent was -0.23 +/- 0.49 D with 75.2% +/- 0.50 D and 95.6% +/- 1.00 D of intended. A loss of two lines of BSCVA occurred in 0.9%, and no eyes lost greater than two lines of BSCVA. Vector analysis showed that 99% of the intended cylinder was corrected on average with a mean angle of error of 4.2 degrees. Refractive stability was achieved between 1 and 3 months in 97.5% of spherical eyes and 99.4% of astigmatic eyes and confirmed between 3 and 6 months in 100% of both spherical and astigmatic eyes. CONCLUSIONS: Eyes treated for myopia up to -11 D of spherical equivalent with or without astigmatism up to -5 D show early refractive stability, good UCVA outcomes, no significant loss of BSCVA, accurate correction of astigmatism, and slight undercorrection without a change from the photorefractive keratectomy algorithm and with a single treatment.

Monocular diplopia related to asymmetric corneal topography after laser in situ keratomileusis.

PURPOSE: To show a specific relationship between monocular diplopia and corneal refractive asymmetry after laser in situ keratomileusis (LASIK). METHODS: One hundred thirty-eight eyes of 98 patients who underwent LASIK for myopia between -2.12 and -17.75 D were examined under room-lighted conditions. We examined 51 eyes at 2 weeks, 46 eyes at 3 months, 32 eyes at 6 months, and 9 eyes at 1 year after LASIK. We attempted to correlate the presence of monocular diplopia with their corneal topographical features. RESULTS: Eight eyes of five patients (five eyes at 2 weeks, three eyes at 3 months after LASIK) produced symptoms of monocular diplopia. These symptomatic patients had a common corneal topographical feature caused by decentralized or inhomogeneous ablation. Every pupillary area in the patients' topographies contained steeper and flatter areas. The range of refractive power variation in these asymmetric areas was at least 1.50 D. The location of the secondary image correlated with the direction of the steeper area in all eight eyes. Pinhole viewing eliminated or reduced the prominence of secondary images in every case. CONCLUSION: Monocular diplopia following LASIK appears to correlate with postoperative corneal refractive power variation inside the pupillary area, caused by decentralized or inhomogeneous ablation.

Drosophila dec-1 eggshell proteins are differentially distributed via a multistep extracellular processing and localization pathway.

In Drosophila the multilayered eggshell forms during late oogenesis between the oocyte and the overlaying follicle cells. Proper eggshell assembly requires wild-type dec-1 gene function. Alternatively spliced dec-1 transcripts encode three proproteins that are cleaved extracellularly in a stage-specific manner to at least five distinct derivatives. Using polyclonal antibodies raised against fusion proteins containing different regions of the dec-1 proteins, we have localized several dec-1 derivatives in the assembling and completed eggshell. Although all of the dec-1 derivatives are generated in the oocyte proximal vitelline membrane layer, they are differentially distributed in the mature egg. Some derivatives are gradually released from the vitelline membrane and become localized within distinct regions of the chorion, while others are taken up by the oocyte or become concentrated in the endochorionic spaces or cavities. The diverse distributions of the dec-1 derivatives suggest that each derivative plays a distinct role in eggshell assembly. These results also suggest that the vitelline membrane layer, by acting as a transient storage site, may control the availability of molecules active in eggshell assembly and by extension perhaps other follicle cell products important in early embryonic pattern formation.

Morphogenesis of the eggshell in Drosophila.

The Drosophila eggshell is a specialized extracellular matrix that forms between the oocyte and overlaying somatic follicle cells during the latter stages of oogenesis. Largely proteinaceous, the eggshell is a highly organized multilayered structure with regional specializations designed to perform a variety of functions. Production of a functional eggshell features: (1) the differentiation of subsets of follicle cells in response to ovarian signals, (2) directed migrations of the follicle cells within the developing egg chamber, (3) expression of eggshell structural genes by the follicle cells in a defined temporal and spatial order, (4) postdepositional modifications of the eggshell proteins including several temporally regulated proteolytic cleavage events, and (5) regulated trafficking of several eggshell proteins in the assembling structure. By exploiting the genetic advantages of Drosophila and using evolution as a guide, the eggshell provides an excellent experimental system to study, in vivo, molecular mechanisms used to regulate protein-protein interactions throughout the assembly of a complex extracellular architecture in a developing organism.