The Experts below are selected from a list of 57 Experts worldwide ranked by ideXlab platform
Robert E. Ward - One of the best experts on this subject based on the ideXlab platform.
-
Septate Junction proteins are required for egg elongation and border cell migration during oogenesis in Drosophila
G3 Genes|Genomes|Genetics, 2021Co-Authors: Haifa Alhadyian, D Shoaib, Robert E. WardAbstract:Abstract Protein components of the invertebrate Occluding Junction—known as the septate Junction (SJ) - are required for morphogenetic developmental events during embryogenesis in Drosophila melanogaster. In order to determine whether SJ proteins are similarly required for morphogenesis during other developmental stages, we investigated the localization and requirement of four representative SJ proteins during oogenesis: Contactin, Macroglobulin complement-related, Neurexin IV, and Coracle. A number of morphogenetic processes occur during oogenesis, including egg elongation, formation of dorsal appendages, and border cell migration. We found that all four SJ proteins are expressed in egg chambers throughout oogenesis, with the highest and most sustained levels in the follicular epithelium (FE). In the FE, SJ proteins localize along the lateral membrane during early and mid-oogenesis, but become enriched in an apical-lateral domain (the presumptive SJ) by stage 10B. SJ protein relocalization requires the expression of other SJ proteins, as well as Rab5 and Rab11 in a manner similar to SJ biogenesis in the embryo. Knocking down the expression of these SJ proteins in follicle cells throughout oogenesis results in egg elongation defects and abnormal dorsal appendages. Similarly, reducing the expression of SJ genes in the border cell cluster results in border cell migration defects. Together, these results demonstrate an essential requirement for SJ genes in morphogenesis during oogenesis, and suggests that SJ proteins may have conserved functions in epithelial morphogenesis across developmental stages. Article Summary: Septate Junction (SJ) proteins are essential for forming an Occluding Junction in epithelial tissues in Drosophila melanogaster, and also for morphogenetic events that occur prior to the formation of the Junction during embryogenesis. Here we show that SJ proteins are expressed in the follicular epithelium of egg chambers during oogenesis and are required for morphogenetic events including egg elongation, dorsal appendages formation, and border cell migration. Additionally, the formation of SJs during oogenesis is similar to that in embryonic epithelia.
-
Expanding the Junction: New Insights into Non-Occluding Roles for Septate Junction Proteins during Development.
Journal of developmental biology, 2021Co-Authors: Clinton Rice, Sonia Hall, Haifa Alhadyian, Robert E. WardAbstract:The septate Junction (SJ) provides an Occluding function for epithelial tissues in invertebrate organisms. This ability to seal the paracellular route between cells allows internal tissues to create unique compartments for organ function and endows the epidermis with a barrier function to restrict the passage of pathogens. Over the past twenty-five years, numerous investigators have identified more than 30 proteins that are required for the formation or maintenance of the SJs in Drosophila melanogaster, and have determined many of the steps involved in the biogenesis of the Junction. Along the way, it has become clear that SJ proteins are also required for a number of developmental events that occur throughout the life of the organism. Many of these developmental events occur prior to the formation of the Occluding Junction, suggesting that SJ proteins possess non-Occluding functions. In this review, we will describe the composition of SJs, taking note of which proteins are core components of the Junction versus resident or accessory proteins, and the steps involved in the biogenesis of the Junction. We will then elaborate on the functions that core SJ proteins likely play outside of their role in forming the Occluding Junction and describe studies that provide some cell biological perspectives that are beginning to provide mechanistic understanding of how these proteins function in developmental contexts.
-
septate Junction proteins are required for egg elongation and border cell migration during oogenesis in drosophila
bioRxiv, 2020Co-Authors: H Alhadyian, D Shoaib, Robert E. WardAbstract:Protein components of the invertebrate Occluding Junction - known as the septate Junction (SJ) - are required for morphogenetic developmental events during embryogenesis in Drosophila melanogaster. In order to determine whether SJ proteins are similarly required for morphogenesis during other developmental stages, we investigated the localization and requirement of four representative SJ proteins during oogenesis: Contactin, Macroglobulin complement-related, Neurexin IV, and Coracle. A number of morphogenetic processes occur during oogenesis, including egg elongation, formation of dorsal appendages, and border cell migration. We found that all four SJ proteins are expressed in the egg throughout oogenesis, with the highest and most sustained levels in the follicular epithelium (FE). In the FE, SJ proteins localize along the lateral membrane during early and mid-oogenesis, but become enriched in an apical-lateral domain (the presumptive SJ) by stage 10b. SJ protein relocalization requires the expression of other SJ proteins, as well as rab5 and rab11 in a manner similar to SJ biogenesis in the embryo. Knocking down the expression of these SJ proteins in follicle cells throughout oogenesis results in egg elongation defects and abnormal dorsal appendages. Similarly, reducing the expression of SJ genes in the border cell cluster results in border cell migration defects. Together, these results demonstrate an essential requirement for SJ genes in morphogenesis during oogenesis, and suggests that SJ proteins may have conserved functions in epithelial morphogenesis across developmental stages. Article SummarySeptate Junction (SJ) proteins are essential for forming an Occluding Junction in epithelial tissues of Drosophila melanogaster. SJ proteins are also required for morphogenetic events during embryogenesis prior to the formation of an Occluding Junction. To determine if SJ proteins function in morphogenesis at other developmental stages, we examined their function during oogenesis, and found that SJ proteins are expressed in the follicular epithelium of the egg chamber and are required for egg elongation, dorsal appendages formation, and border cell migration. Additionally, we found that the formation of SJs in oogenesis is similar to that in embryonic epithelia.
-
Septate Junction Proteins Play Essential Roles in Morphogenesis Throughout Embryonic Development in Drosophila
G3 (Bethesda Md.), 2016Co-Authors: Sonia Hall, Robert E. WardAbstract:The septate Junction (SJ) is the Occluding Junction found in the ectodermal epithelia of invertebrate organisms, and is essential to maintain chemically distinct compartments in epithelial organs, to provide the blood–brain barrier in the nervous system, and to provide an important line of defense against invading pathogens. More than 20 genes have been identified to function in the establishment or maintenance of SJs in Drosophila melanogaster. Numerous studies have demonstrated the cell biological function of these proteins in establishing the Occluding Junction, whereas very few studies have examined further developmental roles for them. Here we examined embryos with mutations in nine different core SJ genes and found that all nine result in defects in embryonic development as early as germ band retraction, with the most penetrant defect observed in head involution. SJ genes are also required for cell shape changes and cell rearrangements that drive the elongation of the salivary gland during midembryogenesis. Interestingly, these developmental events occur at a time prior to the formation of the Occluding Junction, when SJ proteins localize along the lateral membrane and have not yet coalesced into the region of the SJ. Together, these observations reveal an underappreciated role for a large group of SJ genes in essential developmental events during embryogenesis, and suggest that the function of these proteins in facilitating cell shape changes and rearrangements is independent of their role in the Occluding Junction.
Stefan Luschnig - One of the best experts on this subject based on the ideXlab platform.
-
Transient opening of tricellular vertices controls paracellular transport through the follicle epithelium during Drosophila oogenesis
2020Co-Authors: Jone Isasti-sanchez, Fenja Münz-zeise, Stefan LuschnigAbstract:Abstract Paracellular permeability is regulated to allow solute transport or migration of cells across epithelial or endothelial barriers. However, how Occluding Junction dynamics controls paracellular permeability is poorly understood. Here we describe patency, a developmentally regulated process in Drosophila oogenesis, during which cell vertices in the follicle epithelium open transiently to allow paracellular transport of yolk proteins for uptake by the oocyte. We show that the sequential removal of E-Cadherin, N-Cadherin, NCAM/Fasciclin-2 and Sidekick from vertices precedes their basal-to-apical opening, while the subsequent assembly of tricellular Occluding Junctions terminates patency and seals the paracellular barrier. E-Cadherin-based adhesion is required to limit paracellular channel size, whereas stabilized adherens Junctions, prolonged NCAM/Fasciclin-2 expression, impeded endocytosis, or increased actomyosin contractility prevent patency. Our findings reveal a key role of cell vertices as gateways controlling paracellular transport, and demonstrate that the dynamic regulation of adhesion and actomyosin contractility at vertices governs epithelial barrier properties.
-
the transmembrane protein macroglobulin complement related is essential for septate Junction formation and epithelial barrier function in drosophila
Development, 2014Co-Authors: Tilmann Batz, Dominique Forster, Stefan LuschnigAbstract:Occluding cell-cell Junctions in epithelia form physical barriers that separate different membrane domains, restrict paracellular diffusion and prevent pathogens from spreading across tissues. In invertebrates, these functions are provided by septate Junctions (SJs), the functional equivalent of vertebrate tight Junctions. How the diverse functions of SJs are integrated and modulated in a multiprotein complex is not clear, and many SJ components are still unknown. Here we report the identification of Macroglobulin complement-related (Mcr), a member of the conserved α-2-macroglobulin (α2M) complement protein family, as a novel SJ-associated protein in Drosophila. Whereas α2M complement proteins are generally known as secreted factors that bind to surfaces of pathogens and target them for phagocytic uptake, Mcr represents an unusual α2M protein with a predicted transmembrane domain. We show that Mcr protein localizes to lateral membranes of epithelial cells, where its distribution overlaps with SJs. Several SJ components are required for the correct localization of Mcr. Conversely, Mcr is required in a cell-autonomous fashion for the correct membrane localization of SJ components, indicating that membrane-bound rather than secreted Mcr isoforms are involved in SJ formation. Finally, we show that loss of Mcr function leads to morphological, ultrastructural and epithelial barrier defects resembling mutants lacking SJ components. Our results, along with previous findings on the role of Mcr in phagocytosis, suggest that Mcr plays dual roles in epithelial barrier formation and innate immunity. Thus, Mcr represents a novel paradigm for investigating functional links between Occluding Junction formation and pathogen defense mechanisms.
Haifa Alhadyian - One of the best experts on this subject based on the ideXlab platform.
-
Septate Junction proteins are required for egg elongation and border cell migration during oogenesis in Drosophila
G3 Genes|Genomes|Genetics, 2021Co-Authors: Haifa Alhadyian, D Shoaib, Robert E. WardAbstract:Abstract Protein components of the invertebrate Occluding Junction—known as the septate Junction (SJ) - are required for morphogenetic developmental events during embryogenesis in Drosophila melanogaster. In order to determine whether SJ proteins are similarly required for morphogenesis during other developmental stages, we investigated the localization and requirement of four representative SJ proteins during oogenesis: Contactin, Macroglobulin complement-related, Neurexin IV, and Coracle. A number of morphogenetic processes occur during oogenesis, including egg elongation, formation of dorsal appendages, and border cell migration. We found that all four SJ proteins are expressed in egg chambers throughout oogenesis, with the highest and most sustained levels in the follicular epithelium (FE). In the FE, SJ proteins localize along the lateral membrane during early and mid-oogenesis, but become enriched in an apical-lateral domain (the presumptive SJ) by stage 10B. SJ protein relocalization requires the expression of other SJ proteins, as well as Rab5 and Rab11 in a manner similar to SJ biogenesis in the embryo. Knocking down the expression of these SJ proteins in follicle cells throughout oogenesis results in egg elongation defects and abnormal dorsal appendages. Similarly, reducing the expression of SJ genes in the border cell cluster results in border cell migration defects. Together, these results demonstrate an essential requirement for SJ genes in morphogenesis during oogenesis, and suggests that SJ proteins may have conserved functions in epithelial morphogenesis across developmental stages. Article Summary: Septate Junction (SJ) proteins are essential for forming an Occluding Junction in epithelial tissues in Drosophila melanogaster, and also for morphogenetic events that occur prior to the formation of the Junction during embryogenesis. Here we show that SJ proteins are expressed in the follicular epithelium of egg chambers during oogenesis and are required for morphogenetic events including egg elongation, dorsal appendages formation, and border cell migration. Additionally, the formation of SJs during oogenesis is similar to that in embryonic epithelia.
-
Expanding the Junction: New Insights into Non-Occluding Roles for Septate Junction Proteins during Development.
Journal of developmental biology, 2021Co-Authors: Clinton Rice, Sonia Hall, Haifa Alhadyian, Robert E. WardAbstract:The septate Junction (SJ) provides an Occluding function for epithelial tissues in invertebrate organisms. This ability to seal the paracellular route between cells allows internal tissues to create unique compartments for organ function and endows the epidermis with a barrier function to restrict the passage of pathogens. Over the past twenty-five years, numerous investigators have identified more than 30 proteins that are required for the formation or maintenance of the SJs in Drosophila melanogaster, and have determined many of the steps involved in the biogenesis of the Junction. Along the way, it has become clear that SJ proteins are also required for a number of developmental events that occur throughout the life of the organism. Many of these developmental events occur prior to the formation of the Occluding Junction, suggesting that SJ proteins possess non-Occluding functions. In this review, we will describe the composition of SJs, taking note of which proteins are core components of the Junction versus resident or accessory proteins, and the steps involved in the biogenesis of the Junction. We will then elaborate on the functions that core SJ proteins likely play outside of their role in forming the Occluding Junction and describe studies that provide some cell biological perspectives that are beginning to provide mechanistic understanding of how these proteins function in developmental contexts.
D Shoaib - One of the best experts on this subject based on the ideXlab platform.
-
Septate Junction proteins are required for egg elongation and border cell migration during oogenesis in Drosophila
G3 Genes|Genomes|Genetics, 2021Co-Authors: Haifa Alhadyian, D Shoaib, Robert E. WardAbstract:Abstract Protein components of the invertebrate Occluding Junction—known as the septate Junction (SJ) - are required for morphogenetic developmental events during embryogenesis in Drosophila melanogaster. In order to determine whether SJ proteins are similarly required for morphogenesis during other developmental stages, we investigated the localization and requirement of four representative SJ proteins during oogenesis: Contactin, Macroglobulin complement-related, Neurexin IV, and Coracle. A number of morphogenetic processes occur during oogenesis, including egg elongation, formation of dorsal appendages, and border cell migration. We found that all four SJ proteins are expressed in egg chambers throughout oogenesis, with the highest and most sustained levels in the follicular epithelium (FE). In the FE, SJ proteins localize along the lateral membrane during early and mid-oogenesis, but become enriched in an apical-lateral domain (the presumptive SJ) by stage 10B. SJ protein relocalization requires the expression of other SJ proteins, as well as Rab5 and Rab11 in a manner similar to SJ biogenesis in the embryo. Knocking down the expression of these SJ proteins in follicle cells throughout oogenesis results in egg elongation defects and abnormal dorsal appendages. Similarly, reducing the expression of SJ genes in the border cell cluster results in border cell migration defects. Together, these results demonstrate an essential requirement for SJ genes in morphogenesis during oogenesis, and suggests that SJ proteins may have conserved functions in epithelial morphogenesis across developmental stages. Article Summary: Septate Junction (SJ) proteins are essential for forming an Occluding Junction in epithelial tissues in Drosophila melanogaster, and also for morphogenetic events that occur prior to the formation of the Junction during embryogenesis. Here we show that SJ proteins are expressed in the follicular epithelium of egg chambers during oogenesis and are required for morphogenetic events including egg elongation, dorsal appendages formation, and border cell migration. Additionally, the formation of SJs during oogenesis is similar to that in embryonic epithelia.
-
septate Junction proteins are required for egg elongation and border cell migration during oogenesis in drosophila
bioRxiv, 2020Co-Authors: H Alhadyian, D Shoaib, Robert E. WardAbstract:Protein components of the invertebrate Occluding Junction - known as the septate Junction (SJ) - are required for morphogenetic developmental events during embryogenesis in Drosophila melanogaster. In order to determine whether SJ proteins are similarly required for morphogenesis during other developmental stages, we investigated the localization and requirement of four representative SJ proteins during oogenesis: Contactin, Macroglobulin complement-related, Neurexin IV, and Coracle. A number of morphogenetic processes occur during oogenesis, including egg elongation, formation of dorsal appendages, and border cell migration. We found that all four SJ proteins are expressed in the egg throughout oogenesis, with the highest and most sustained levels in the follicular epithelium (FE). In the FE, SJ proteins localize along the lateral membrane during early and mid-oogenesis, but become enriched in an apical-lateral domain (the presumptive SJ) by stage 10b. SJ protein relocalization requires the expression of other SJ proteins, as well as rab5 and rab11 in a manner similar to SJ biogenesis in the embryo. Knocking down the expression of these SJ proteins in follicle cells throughout oogenesis results in egg elongation defects and abnormal dorsal appendages. Similarly, reducing the expression of SJ genes in the border cell cluster results in border cell migration defects. Together, these results demonstrate an essential requirement for SJ genes in morphogenesis during oogenesis, and suggests that SJ proteins may have conserved functions in epithelial morphogenesis across developmental stages. Article SummarySeptate Junction (SJ) proteins are essential for forming an Occluding Junction in epithelial tissues of Drosophila melanogaster. SJ proteins are also required for morphogenetic events during embryogenesis prior to the formation of an Occluding Junction. To determine if SJ proteins function in morphogenesis at other developmental stages, we examined their function during oogenesis, and found that SJ proteins are expressed in the follicular epithelium of the egg chamber and are required for egg elongation, dorsal appendages formation, and border cell migration. Additionally, we found that the formation of SJs in oogenesis is similar to that in embryonic epithelia.
Tilmann Batz - One of the best experts on this subject based on the ideXlab platform.
-
the transmembrane protein macroglobulin complement related is essential for septate Junction formation and epithelial barrier function in drosophila
Development, 2014Co-Authors: Tilmann Batz, Dominique Forster, Stefan LuschnigAbstract:Occluding cell-cell Junctions in epithelia form physical barriers that separate different membrane domains, restrict paracellular diffusion and prevent pathogens from spreading across tissues. In invertebrates, these functions are provided by septate Junctions (SJs), the functional equivalent of vertebrate tight Junctions. How the diverse functions of SJs are integrated and modulated in a multiprotein complex is not clear, and many SJ components are still unknown. Here we report the identification of Macroglobulin complement-related (Mcr), a member of the conserved α-2-macroglobulin (α2M) complement protein family, as a novel SJ-associated protein in Drosophila. Whereas α2M complement proteins are generally known as secreted factors that bind to surfaces of pathogens and target them for phagocytic uptake, Mcr represents an unusual α2M protein with a predicted transmembrane domain. We show that Mcr protein localizes to lateral membranes of epithelial cells, where its distribution overlaps with SJs. Several SJ components are required for the correct localization of Mcr. Conversely, Mcr is required in a cell-autonomous fashion for the correct membrane localization of SJ components, indicating that membrane-bound rather than secreted Mcr isoforms are involved in SJ formation. Finally, we show that loss of Mcr function leads to morphological, ultrastructural and epithelial barrier defects resembling mutants lacking SJ components. Our results, along with previous findings on the role of Mcr in phagocytosis, suggest that Mcr plays dual roles in epithelial barrier formation and innate immunity. Thus, Mcr represents a novel paradigm for investigating functional links between Occluding Junction formation and pathogen defense mechanisms.
