Biomedical subjects

S Zusman

Publications and source records attributed to S Zusman.

10 recordsLinked to original sources

PubMed1999

wing blister, a new Drosophila laminin alpha chain required for cell adhesion and migration during embryonic and imaginal development.

We report the molecular and functional characterization of a new alpha chain of laminin in Drosophila. The new laminin chain appears to be the Drosophila counterpart of both vertebrate alpha2 (also called merosin) and alpha1 chains, with a slightly higher degree of homology to alpha2, suggesting that this chain is an ancestral version of both alpha1 and alpha2 chains. During embryogenesis, the protein is associated with basement membranes of the digestive system and muscle attachment sites, and during larval stage it is found in a specific pattern in wing and eye discs. The gene is assigned to a locus called wing blister (wb), which is essential for embryonic viability. Embryonic phenotypes include twisted germbands and fewer pericardial cells, resulting in gaps in the presumptive heart and tracheal trunks, and myotubes detached from their target muscle attachment sites. Most phenotypes are in common with those observed in Drosophila laminin alpha3, 5 mutant embryos and many are in common with those observed in integrin mutations. Adult phenotypes show blisters in the wings in viable allelic combinations, similar to phenotypes observed in integrin genes. Mutation analysis in the eye demonstrates a function in rhabdomere organization. In summary, this new laminin alpha chain is essential for embryonic viability and is involved in processes requiring cell migration and cell adhesion.

Alleles↗

PubMed1998

Requirements for the cytoplasmic domain of the alphaPS1, alphaPS2 and betaPS integrin subunits during Drosophila development.

The integrins are a family of transmembrane heterodimeric proteins that mediate adhesive interactions and participate in signaling across the plasma membrane. In this study we examine the functional significance of the cytoplasmic domains of the alphaPS1, alphaPS2 and betaPS subunits of the Drosophila Position Specific (PS) integrin family by analyzing the relationship between cytoplasmic domain structure and function in the context of a developing organism. By examining the ability of ssPS molecules lacking the cytoplasmic domain to rescue embryonic abnormalities associated with PS integrin loss, we find that although many embryonic events require the betaPS cytoplasmic domain, this portion of the molecule is not required for at least two processes requiring PS integrins: formation of midgut constrictions and maintaining germband integrity. Furthermore, our studies demonstrate that mutant proteins affecting four highly conserved amino acid residues in the cytoplasmic tail function with different efficiencies during embryonic development, suggesting that interaction of PS integrins with cytoplasmic ligands is developmentally modulated during embryogenesis. We have also examined the ability of alphaPS1 and alphaPS2 to function without their cytoplasmic domains. By analyzing the ability of transgenes producing truncated alphaPS molecules to rescue abnormalities associated with integrin loss, we find that the cytoplasmic tail of alphaPS2 is essential for both embryonic and postembryonic processes, while this portion of alphaPS1 is not required for function in the wing and in the retina. Furthermore, temperature-shift experiments suggest roles for the alphaPS2 cytoplasmic domain in signaling events occurring in the developing wing.

Amino Acid Sequence↗

PubMed1997

A novel alpha integrin subunit associates with betaPS and functions in tissue morphogenesis and movement during Drosophila development.

We have identified a novel alpha integrin subunit in Drosophila, that associates with betaPS integrin. We report the temporal expression of the gene encoding this integrin subunit, which we have called alphaPS3, throughout development and the localization of its expression during embryogenesis. AlphaPS3 RNA was localized to tissues undergoing invagination, tissue movement and morphogenesis such as salivary gland, trachea, midgut, dorsal vessel, midline of the ventral nerve cord, amnioserosa and the amnioproctodeal invagination. AlphaPS3 DNA localized to the chromosomal vicinity of scab (scb), previously identified by a failure of dorsal closure. Embryos homozygous for the 119 allele of scb had no detectable alphaPS3 RNA and the 1035 allele of scb contains a P element inserted just 5' of the coding region for the shorter of the gene's two transcripts. Furthermore, mutations in the scb locus exhibit additional defects corresponding to sites of alphaPS3 transcription, including abnormal salivary glands, mislocalization of the pericardial cells and interrupted trachea. Removal of both maternal and zygotic betaPS produced similar defects, indicating that these two integrin subunits associate in vivo and function in the movement and morphogenesis of tissues during development in Drosophila. Phenotypic similarities suggest that laminin A is a potential ligand for this integrin, at least in some tissues.

Amino Acid Sequence↗

PubMed1996

Alternatively spliced forms of the Drosophila alphaPS2 subunit of integrin are sufficient for viability and can replace the function of the alphaPS1 subunit of integrin in the retina.

The Drosophila inflated (if) gene encodes the alphaPS2 subunit of the PS family of integrins. The if transcript is spliced such that alphaPS2 is found in two alternative forms, alphaPS2(C) and alphaPS2(m8), which differ by 25 amino acid residues in a region shown to affect cation requirements and ligand specificity. In this study, we examine the functional significance of the protein isoforms of if by analyzing the ability of transgenes producing only one isoform to rescue developmental abnormalities associated with complete loss of PS2 integrin. We find that either form of alphaPS2 is sufficient to rescue if- animals to viability; however, the alphaPS2(C) form promotes higher survival of the organism. Furthermore, these studies suggest distinct roles for alphaPS2(C) and alphaPS2(m8) during development. When expressed in the developing wing, alphaPS2(m8) is more efficient at rescuing the if wing blister phenotype than is alphaPS2(C). Expression of alphaPS2(C) in the eye produces dominant disruption of photoreceptor organization. We have also examined the ability of alphaPS2 and alphaPS1 to maintain photoreceptor organization in the Drosophila retina. Clonal analysis of sectioned eyes suggests a requirement for alphaPS1, but not alphaPS2. However, ectopic expression of if(m8) or if(C) shows that either splice form Of alphaPS2 can functionally replace alphaPS1 and rescue the mew eye phenotype.

Alternative Splicing↗

PubMed1995

Functions for PS integrins in tissue adhesion, migration, and shape changes during early embryonic development in Drosophila.

The position-specific (PS) integrins of Drosophila are a family of cell surface heterodimers that function as receptors for extracellular matrix molecules. In this study we used time-lapse videomicroscopy to examine living embryos lacking both maternal and zygotic expression of the genes that encode the alpha PS1, alpha PS2, and beta PS integrin subunits. We demonstrate roles for these molecules as early as gastrulation. Abnormalities in mutant embryos include: separation and twisting of the embryonic germband, abnormal shape and migration of midgut primordia, irregular visceral mesoderm, detachment of amnioserosa cells, rupture of the cuticle along the dorsal midline, lack of midgut constriction, and detachment of somatic muscles. These observations suggest multiple roles for PS integrins in the adhesion of cells and in the formation, organization, and migration of embryonic tissues. We also show that although alpha PS1 beta PS and alpha PS2 beta PS are often expressed in adjacent embryonic tissues, this distribution does not necessarily reflect equivalent requirements. Furthermore, the complete loss of both alpha subunits does not produce all of the phenotypes observed in embryos lacking beta PS. This suggests that alpha PS1 beta PS and alpha PS2 beta PS are not required in all embryonic processes utilizing PS integrins.

Animals↗

PubMed1995

Nonequivalent requirements for PS1 and PS2 integrin at cell attachments in Drosophila: genetic analysis of the alpha PS1 integrin subunit.

We report on the generation and phenotype of mutant alleles of multiple edematous wings (mew), the gene encoding the alpha PS1 subunit of the PS1 integrin of Drosophila. None of the six alleles examined makes detectable protein, and one allele results from a chromosome break near the middle of the translated sequence, so we are confident that we have described the null phenotype. In contrast to if (alpha PS2) and mys (beta PS) mutants, most mutant mew embryos hatch, to die as larvae. Mutant mew embryos display abnormal gut morphogenesis but, unlike mys or if embryos, there is no evidence of defects in the somatic muscles. Thus, the complementary distributions of PS1 (alpha PS1 beta PS) and PS2 (alpha PS2 beta PS) integrin on tendon cells and muscle, respectively, do not reflect equivalent requirements at the myotendinous junction. Dorsal herniation, characteristic of the mys lethal phenotype, is not observed in mew or in mew if embryos. Clonal analysis experiments indicate that eye morphogenesis is disrupted in mew clones, but if clones in the eye are relatively normal in morphology. Adult wings display blisters around large dorsal but not ventral mew clones. In contrast to dorsal mys clones, small mew patches do not necessarily display morphogenetic abnormalities. Thus, another integrin in addition to PS1 appears to function on the dorsal wing surface.

Alleles↗

PubMed1994

Functions of the cytoplasmic domain of the beta PS integrin subunit during Drosophila development.

Integrins constitute a family of membrane-spanning, heterodimeric proteins that mediate adhesive interactions between cells and surrounding extracellular matrices (or other cells) and participate in signal transduction. We are interested in assessing integrin functions in the context of developing Drosophila melanogaster. This report, using mutants of the beta PS subunit encoded by the myospheroid (mys) locus, analyzes the relationships between integrin protein structure and developmental functions in an intact organism. As a first step in this analysis, we demonstrated the ability of a fragment of wild-type mys genomic DNA, introduced into the germ line in a P-element vector P[mys+], to rescue phenotypes attributed to lack of (or defects in) the endogenous beta PS during several discrete morphogenetic events. We then produced in vitro a series of modifications of the wild-type P[mys+] transposon, which encode beta PS derivatives with mutations within the small and highly conserved cytoplasmic domain. In vivo analysis of these mutant transposons led to the following conclusions. (1) The cytoplasmic tail of beta PS is essential for all developmental functions of the protein that were assayed. (2) An intron at a conserved position in the DNA sequence encoding the cytoplasmic tail is thought to participate in important alternative splicing events in vertebrate beta integrin subunit genes, but is not required for the developmental functions of the mys gene assayed here. (3) Phosphorylation on two conserved tyrosines found in the C terminus of the beta PS cytoplasmic tail is not necessary for the tested developmental functions. (4) Four highly conserved amino acid residues found in the N-terminal portion of the cytoplasmic tail are important but not critical for the developmental functions of beta PS; furthermore, the efficiencies with which these mutant proteins function during different morphogenetic processes vary greatly, strongly suggesting that the cytoplasmic interactions involving PS integrins are developmentally modulated.

Amino Acid Sequence↗

PubMed1993

Analyses of PS integrin functions during Drosophila development.

The Drosophila position-specific (PS) antigens are homologues of the vertebrate integrins, a family of transmembrane proteins that function in cell-matrix and cell-cell adhesion. The common beta subunit of PS integrins (PS beta) is encoded by the lethal(l)myospheroid gene (mys) and is required during wing, eye and muscle development. By expressing PS beta protein at defined developmental periods, we have shown that PS integrins are required throughout pupation, but not earlier, for normal development of wings. In contrast, the key requirement for PS integrins in eye development occurs only in the late pupa. Furthermore, PS integrins are apparently not required for the differentiation of the ommatidial cells; only for their organization. These results are consistent with roles for PS integrins in the interactions between the wing epithelia during the two phases of pupal wing expansion and in maintaining the attachment of a fully formed fenestrated membrane to the basement membrane of the retina. We have also examined the functional significance of alternative splicing of the transcript of the mys gene using P element-mediated transformation to introduce transgenes producing only one of the two spliced forms of PS beta. We find that either form is sufficient to rescue postembryonic mys phenotypes in the wing, eye and muscle but that both of the two splice forms are necessary to rescue the mys embryonic defects. This result indicates a requirement for the alternative splicing of mys during embryogenesis. The location of the alternative exons suggests that the two forms of the PS beta integrin subunit may interact with alternative alpha subunits and/or ligands.

Animals↗

PubMed1993

Dental underemployment: a study of uncontrolled dental manpower immigration.

In the 1980s three studies were conducted in Israel utilising different methods of dental manpower evaluations. All identified a large future surplus of dentists. The current study re-evaluates the manpower supply and discusses possible solutions. A random sample of 800 dentists was approached by three mailings and a telephone call follow-up with a response of 49.7 per cent. Almost 90 per cent of dentists reported an undersupply of patients, with a mean working load of 26.3 hours/week, but being willing to add up to 3.4 working hours/week. The oversupply of dentists has been dramatically affected by the addition of almost 1000 dentists who emigrated to Israel in 1991-92. To prevent a significant unemployment rate among dentists and an uncontrolled free market, it is urgently suggested for the benefit of both provider and consumer that; the demand for services be increased and additional financing of dental care be made available, that the total number of dentists be decreased by various measures and that their geographical distribution be improved. If necessary limits should be placed on the number of practices or the number of patients permitted per practice.

Adult↗

PubMed1990

Requirements for integrins during Drosophila development.

The common beta subunit of the PS antigens of Drosophila is homologous with vertebrate integrins and is encoded by the lethal(1)myospheroid gene. We have generated flies mosaic for wild-type and mutant alleles of lethal(1)myospheroid using adult gynandromorphs and radiation-induced somatic crossing over. The defects observed in the gynandromorphs demonstrate widespread requirements for PS integrins during development especially in ventrally derived structures, which also show strong expression of PS beta integrin. Smaller lethal(1)myospheroid clones induced during larval development result in blister and vein defects in the wings and aberrant development of photoreceptor cells, demonstrating roles for PS integrins during development of both wings and eyes. PS integrins are required for the close apposition of the dorsal and ventral wing epithelia and for the proper arrangement of photoreceptor cells. However, many other adhesive and morphogenetic processes proceed normally in the absence of integrins containing the beta subunit encoded by lethal(1)myospheroid.

Animals↗