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A Nose

Publications and source records attributed to A Nose.

At least 37 records · Page 2Linked to original sources
PubMed1997

Mindin/F-spondin family: novel ECM proteins expressed in the zebrafish embryonic axis.

F-spondin is a secreted protein expressed at high levels by the floor plate cells. The C-terminal half of the protein contains six thrombospondin type 1 repeats, while the N-terminal half exhibited virtually no similarity to any other protein until recently, when a Drosophila gene termed M-spondin was cloned; its product was found to share two conserved domains with the N-terminal half of F-spondin. We report the molecular cloning of four zebrafish genes encoding secreted proteins with these conserved domains. Two are zebrafish homologs of F-spondin, while the other two, termed mindin1 and mindin2, encode mutually related novel proteins, which are more related to the Drosophila M-spondin than to F-spondin. During embryonic development, all four genes are expressed in the floor plate cells. In addition to the floor plate, mindin1 is expressed in the hypochord cells, while mindin2 is expressed in the sclerotome cells. When ectopically expressed, Mindin proteins selectively accumulate in the basal lamina, suggesting that Mindins are extracellular matrix (ECM) proteins with high affinity to the basal lamina. We also report the spatial distribution of one of the F-spondin proteins, F-spondin2. F-spondin2 is localized to the thread-like structure in the central canal of the spinal cord, which is likely to correspond to Reissner's fiber known to be present in the vertebrate phylum. In summary, our study has defined a novel gene family of ECM molecules in the vertebrate, all of which may potentially be involved in development of the midline structure.

Amino Acid Sequence↗
PubMed1997

M-spondin, a novel ECM protein highly homologous to vertebrate F-spondin, is localized at the muscle attachment sites in the Drosophila embryo.

The muscle attachment site (MAS) in Drosophila provides a unique and excellent model system to study the mechanism of cell-matrix adhesion in developing organisms. Here, we report on the isolation and characterization of a novel extracellular matrix (ECM) molecule localized at the MAS, encoded by the M-spondin (mspo) gene. M-spondin protein contains a thrombospondin type I repeat (TSR) previously found in a variety of ECM molecules. Furthermore, it shares two conserved domains with F-spondin, a vertebrate ECM molecule with TSRs. The presence of TSR(s) and the two homologous domains thus defines a novel gene family of ECM molecules. The mspo mRNA was expressed by a large subset of muscles in the embryonic body wall. Secreted M-spondin protein diffused and eventually became immobilized at the MAS in late embryos. When expressed in S2 cells, the protein was secreted and became concentrated in the matrix on the surface of the culture dish. Genetic analysis revealed that both deletion mutants and misexpression mutants suffered no obvious developmental defects. We propose that M-spondin, although its function is redundant, is a component of the ECM and mediates mechanical linkage between the muscles and apodemes.

Amino Acid Sequence↗
PubMed1997

The role of the msh homeobox gene during Drosophila neurogenesis: implication for the dorsoventral specification of the neuroectoderm.

Development of the Drosophila central nervous system begins with the delamination of neural and glial precursors, called neuroblasts, from the neuroectoderm. An early and important step in the generation of neural diversity is the specification of individual neuroblasts according to their position. In this study, we describe the genetic analysis of the msh gene which is likely to play a role in this process. The msh/Msx genes are one of the most highly conserved families of homeobox genes. During vertebrate spinal cord development, Msx genes (Msx1-3) are regionally expressed in the dorsal portion of the developing neuroectoderm. Similarly in Drosophila, msh is expressed in two longitudinal bands that correspond to the dorsal half of the neuroectoderm, and subsequently in many dorsal neuroblasts and their progeny. We showed that Drosophila msh loss-of-function mutations led to cell fate alterations of neuroblasts formed in the dorsal aspect of the neuroectoderm, including a possible dorsal-to-ventral fate switch. Conversely, ectopic expression of msh in the entire neuroectoderm severely disrupted the proper development of the midline and ventral neuroblasts. The results provide the first in vivo evidence for the role of the msh/Msx genes in neural development, and support the notion that they may perform phylogenetically conserved functions in the dorsoventral patterning of the neuroectoderm.

Animals↗
PubMed1997

Neuromuscular target recognition by a homophilic interaction of connectin cell adhesion molecules in Drosophila.

Drosophila Connectin (CON) is a cell surface protein of the leucine-rich repeat family. During the formation of neuromuscular connectivity, CON is expressed on the surface of a subset of embryonic muscles and on the growth cones and axons of the motoneurons that innervate these muscles, including primarily SNa motoneurons and their synaptic targets (lateral muscles). In vitro, CON can mediate homophilic cell adhesion. In this study, we generated transgenic lines that ectopically expressed CON on all muscles. In the transformant embryos and larvae, SNa motoneurons often inappropriately innervated a neighboring non-target muscle (muscle 12) that ectopically expressed CON. Furthermore, the ectopic synapse formation was dependent on the endogenous CON expression on the SNa motoneurons. These results show that CON can function as an attractive and homophilic target recognition molecule in vivo.

Animals↗
PubMed1994

Ectopic expression of connectin reveals a repulsive function during growth cone guidance and synapse formation.

Connectin, a cell surface protein of the leucine-rich repeat family in Drosophila, is expressed on the surface of a subset of embryonic muscles (primarily lateral muscles), on the growth cones and axons of the motoneurons that innervate these muscles (primarily SNa motoneurons), and on several associated glial cells. When coupled with its ability to mediate homophilic cell adhesion, these results led to the suggestion that Connectin functions as an attractive signal for SNa pathfinding and targeting. In the present study, we ectopically expressed Connectin on ventral muscles normally innervated by SNb motoneurons. The SNb growth cones change both their morphology and their trajectory when they encounter ectopic Connectin-positive ventral muscles, displaying "bypass," "detour," and "stall" phenotypes. Moreover, SNb synapse formation is prevented by Connectin expression on ventral muscles. These results reveal a repulsive function for Connectin during motoneuron growth cone guidance and synapse formation.

Animals↗
PubMed1992

Connectin: a homophilic cell adhesion molecule expressed on a subset of muscles and the motoneurons that innervate them in Drosophila.

Each abdominal hemisegment in the Drosophila embryo contains a stereotyped array of 30 muscles, each specifically innervated by one or a few motoneurons. We screened 11,000 enhancer trap lines, isolated several expressing beta-galactosidase in small subsets of muscle fibers prior to innervation, and identified two of these as inserts in connectin and Toll, members of the leucine-rich repeat gene family. Connectin contains a signal sequence, ten leucine-rich repeats, and a putative phosphatidylinositol membrane linkage; in S2 cells, connectin can mediate homophilic cell adhesion. Connectin is expressed on the surface of eight muscles, the motoneurons that innervate them, and several glial cells along the pathways leading to them. During synapse formation, the protein localizes to synaptic sites; afterward, it largely disappears. Thus, connectin is a novel cell adhesion molecule whose expression suggests a role in target recognition.

Amino Acid Sequence↗
PubMed1990

Localization of specificity determining sites in cadherin cell adhesion molecules.

Cadherins are a group of homophilic intercellular adhesion molecules; each member of this family exhibits binding specificity. Here, we attempted to map the sites for the specificities of these molecules by analyzing adhesives selectivities of the cells that express chimeric and point-mutated E- and P-cadherin. The results showed that the amino-terminal 113 amino acid region is essential to determine the specificities, and within this region we could identify especially important sites in which amino acid substitutions altered the binding specificity of cadherins. We also found that the epitopes for antibodies capable of blocking cadherin action are located in this amino-terminal region.

Amino Acid Sequence↗
PubMed1990

Cadherin-mediated cell-cell adhesion and neurogenesis.

Cadherins constitute a molecular family which confers adhesive specificities on cells. Their expression is spatio-temporally regulated in embryos and the multiple types of cadherins are expressed in the nervous system. The inhibition of cadherin action with antibodies resulted in the perturbation of the histogenesis of neural tissues. The sites for determining the binding specificities of cadherins reside in their amino terminal 113 amino acid region. Possible roles of cadherins associated with these properties in neurogenesis are discussed.

Animals↗
PubMed1989

Neural cadherin: role in selective cell-cell adhesion.

Cadherins are a family of Ca2+-dependent intercellular adhesion molecules. Complementary DNAs encoding mouse neural cadherin (N-cadherin) were cloned, and the cell binding specificity of this molecule was examined. Mouse N-cadherin shows 92 percent similarity in amino acid sequence to the chicken homolog, while it shows 49 percent and 43 percent similarity to epithelial cadherin and to placental cadherin of the same species, respectively. In cell binding assays, mouse N-cadherin did not cross-react with other mouse cadherins, but it did cross-react with chicken N-cadherin. The results indicate that each cadherin type confers distinct adhesive specificities on different cells, and also that the specificity of N-cadherin is conserved between mammalian and avian cells.

Amino Acid Sequence↗
PubMed1989

Cadherin-mediated specific cell adhesion and animal morphogenesis.

Cadherins are a family of transmembrane glycoproteins which are responsible for Ca2+-dependent cell-cell adhesion. Each member of the family displays a unique pattern of tissue distribution. The expression of cadherin molecules in an embryo is spatiotemporally regulated so as to be associated with a variety of morphogenetic events. Antibodies against cadherins perturb the morphogenesis of tissues, indicating their importance in tissue formation. When cells were transfected with cDNAs encoding cadherins, they expressed the exogenous cadherin molecules and these were functional. Using these transfected cells, we tested whether each member of the cadherin family has a binding specificity, and found that cells preferentially adhere to those expressing the identical cadherin type. The cadherin-mediated specific adhesion also occurred in the attachment of neurites to the surface of other cells. These observations suggest that cadherins are crucial for the selective adhesiveness of cells, and thus for the embryonic morphogenetic processes in which specific adhesive interactions of cells are involved.

Animals↗
PubMed1989

Expression and role of E- and P-cadherin adhesion molecules in embryonic histogenesis. I. Lung epithelial morphogenesis.

The role of Ca2+-dependent cell-cell adhesion molecules, E- and P-cadherins, in the histogenesis of mouse embryonic lung was studied. All epithelial cells of the lung express both E- and P-cadherin at the early developmental stage. P-cadherin, however, gradually disappears during development, initially from the main bronchi and eventually from all epithelial cells. When a monoclonal antibody to E-cadherin (ECCD-1) was added to monolayer cultures of lung epithelial cells, it induced a partial disruption of their cell-cell adhesion, while a monoclonal antibody to P-cadherin (PCD-1) showed a subtle effect. A mixture of the two antibodies, however, displayed a synergistic effect. We then tested the effect of the antibodies on the morphogenesis of lung primordia using an organ culture system. In control media, the explants formed typical bronchial trees. In the presence of ECCD-1, the explants grew up at the same rate as in the control, but their morphogenesis was affected. The control explants formed round epithelial lobules with an open luminal space at the tips of the bronchial trees, whereas the lobules of explants incubated with ECCD-1 tended to be flat and devoid of the luminal space. PCD-1 showed a similar but very small effect. A mixture of the two antibodies, however, showed a stronger effect: the branching of epithelia was partially suppressed and the arrangement of epithelial cells was distorted in many places. These results suggest that E- and P-cadherin have a synergistic role in the organization of epithelial cells in lung morphogenesis.

Animals↗
PubMed1989

Expression and role of E- and P-cadherin adhesion molecules in embryonic histogenesis. II. Skin morphogenesis.

Expression and the role of E- and P-cadherin in the histogenesis of the surface epidermis and hair follicles were examined using the upper lip skin of the mouse. P-cadherin is expressed exclusively in the proliferating region of these tissues, that is in the germinative layer of the surface epidermis, the outer root sheath and the hair matrix. E-cadherin is coexpressed in these layers but this molecule was also detected in non-proliferating regions such as the intermediate layer of the surface epidermis and the immature regions of the inner root sheath. Neither P- nor E-cadherin was detected in fully keratinized layers such as the horny layer of the surface epidermis, the outermost layer of the outer root sheath and the mature hair fibres. These two cadherins were not detected in dermal cells. We cultured pieces of the upper lip skin in vitro in the absence or presence of a monoclonal antibody to E-cadherin (ECCD-1) or to P-cadherin (PCD-1). In control cultures, skin morphogenesis normally occurred in a pattern whereby the hair follicles grew and dermal cells were condensed to form the dermal sheath. A mixture of ECCD-1 and PCD-1, however, induced abnormal morphogenesis in the skin in several respects. (1) The cuboidal or columnar arrangement of basal epithelial cells was distorted. (2) Hair follicles were deformed. (3) Condensation of dermal cells was suppressed, causing a homogeneous distribution of these cells. These results suggest that cadherins present in epidermal cells are involved not only in maintaining the arrangement of these cells but also in inducing dermal condensation.

Animals↗
PubMed1988

Expressed recombinant cadherins mediate cell sorting in model systems.

Cadherins are cell-surface glycoproteins responsible for Ca2+-dependent cell-to-cell adhesion. E- or P-cadherin was transfected into L cells, which normally have little cadherin activity, and cellular aggregation of the resulting transfectants was observed to be a function of the cadherin molecule expressed. Transfected cells preferentially adhered to cells expressing the same cadherin subclass. Furthermore, in reconstituted embryonic lung tissue, E-cadherin-expressing L cells were associated with epithelial tubules expressing E-cadherin, while untransfected L cells associated with mesenchymal cells. These results provide the first direct evidence that the differential expression of cadherins can play a role in cell sorting in heterogeneous cell populations.

Agglutination↗
PubMed1988

Identification of a gene family of cadherin cell adhesion molecules.

Cadherins are a group of functionally related glycoproteins responsible for the Ca2+-dependent cell-cell adhesion mechanism. They are divided into subclasses, such as E-, P- and N-cadherin, which are distinct in immunological specificities and tissue distribution. Cell aggregation experiments suggest that these molecules have subclass specificities in cell-cell binding and are involved in selective cell adhesions. Analysis of amino acid sequences deduced from the nucleotide sequences of cDNAs encoding cadherins demonstrated that they are integral membrane proteins and share common sequences throughout their entire length; average similarity in the sequences among them is in a range of 50-60%. This result provided evidence that cadherins constitute a gene family which encodes adhesion molecules with different specificities. We also showed that, when cells with little cadherin activity were transfected with cadherin cDNAs, they acquired the cadherin-mediated adhesion properties.

Animals↗
PubMed1988

Cloning and expression of cDNA encoding a neural calcium-dependent cell adhesion molecule: its identity in the cadherin gene family.

The neural cadherin (N-cadherin) is a Ca2+-dependent cell-cell adhesion molecule detected in neural tissues as well as in non-neural tissues. We report here the nucleotide sequence of the chicken N-cadherin cDNA and the deduced amino acid sequence. The sequence data suggest that N-cadherin has one transmembrane domain which divides the molecule into an extracellular and a cytoplasmic domain; the extracellular domain contains internal repeats of characteristic sequences. When the N-cadherin cDNA connected with virus promoters was transfected into L cells which have no endogenous N-cadherin, the transformants acquired the N-cadherin-mediated aggregating property, indicating that the cloned cDNA contained all information necessary for the cell-cell binding action of this molecule. We then compared the primary structure of N-cadherin with that of other molecules defined as cadherin subclasses. The results showed that these molecules contain common amino acid sequences throughout their entire length, which confirms our hypothesis that cadherins make a gene family.

Amino Acid Sequence↗
PubMed1987

Isolation of placental cadherin cDNA: identification of a novel gene family of cell-cell adhesion molecules.

Ca2+-dependent cell--cell adhesion molecules, termed cadherins, are classified into subclasses with different tissue distributions and distinct cell--cell binding specificities. We report the cloning of cDNA encoding a cadherin present in the placenta which is called P-cadherin. The deduced sequence encodes a polypeptide of 822 amino acids with the characteristic features of integral membrane proteins. A computer search of the amino acid sequence homology of P-cadherin against itself showed that this molecule contains internal repeats in the extracellular domain. Comparison of the primary structure of P-cadherin with that of the epithelial cadherin (E-cadherin) showed that there is 58% homology in their amino acid sequences. These results provide evidence for our hypothesis that cadherins constitute a gene family.

Amino Acid Sequence↗