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M Schachner

Publications and source records attributed to M Schachner.

At least 235 records · Page 13Linked to original sources
PubMed1994

The L2/HNK-1 carbohydrate is preferentially expressed by previously motor axon-associated Schwann cells in reinnervated peripheral nerves.

The carbohydrate epitope L2/HNK-1 (hereafter designated L2) is expressed in the adult mouse by myelinating Schwann cells of ventral roots and muscle nerves, but rarely by those of dorsal roots or cutaneous nerves. Since substrate-coated L2 glycolipids promote outgrowth of cultured motor but not sensory neurons, L2 may thus influence the preferential reinnervation of muscle nerves by regenerating motor axons in vivo. In the present study, we have analyzed the influence of regenerating axons on L2 expression by reinnervated Schwann cells by directing motor or sensory axons into the muscle and cutaneous branches of femoral nerves of 8-week-old mice. We observed that regenerating axons from cutaneous branches did not lead to immunocytochemically detectable L2 expression in muscle or cutaneous nerve branches. Axons regenerating from muscle branches led to a weak L2 expression by few Schwann cells of the cutaneous branch, but provoked a strong L2 expression by many Schwann cells of the muscle branch. Myelinating Schwann cells previously associated with motor axons thus differed from previously sensory axon-associated myelinating Schwann cells in their ability to express L2 when contacted by motor axons. This upregulation of L2 expression during critical stages of reinnervation may provide motor axons regenerating into the appropriate, muscle pathways with an advantage over those regenerating into the inappropriate, sensory pathways.

Animals↗
PubMed1994

The perplexing multifunctionality of janusin, a tenascin-related molecule.

The extracellular matrix glycoprotein janusin, closely related to tenascin in its repeated motifs of epidermal growth factor, fibronectin type III, and fibrinogen-like domains, displays in vitro a broad spectrum of functional diversity. Synthesized by oligodendrocytes and subpopulations of neurons at late developmental stages in the rodent central nervous system, it can be adhesive or antiadhesive, depending on the neural cell type that interacts with it. It promotes neurite outgrowth of some neural cell types, when offered as a uniform culture substrate, but inhibits neurite outgrowth of other neuronal populations. When offered as a sharp substrate boundary in congruence with a permissive substrate, it acts as a barrier for neurite outgrowth. Like tenascin, it can modify the adhesive substrate properties of another extracellular matrix glycoprotein, fibronectin, whereby the smaller, 160 kD component of janusin exerts its effects by interaction with fibronectin and the 180 kD janusin component functionally modifies the fibronectin receptor via a disialoganglioside receptor. In neurons, the antiadhesive and neurite outgrowth inhibiting signal is mediated by the F3/11 immunoglobulin superfamily recognition molecule. In oligodendrocytes, yet another receptor for janusin mediates adhesion and process formation. A prerequisite for any intracellular response to occur is a transient lock-and-key recognition manifesting itself in short-term binding between the interacting partners. As for tenascin, the different functions exerted by janusin are likely to be encoded in the different domains of the janusin molecule, which can act on different receptors, whereby the receiving cell is able to interpret the cell surface trigger in different ways, depending on the particular cell type involved.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[Morphology and development of neural transplants of AMOG-deficient mice].

The adhesion molecule on glia (AMOG) has been reported to function as cell adhesion molecule and also to constitute the beta 2-subunit of the murine Na,K-ATPase. In order to elucidate these functions in vivo, Magyar et al. have generated mice carrying a targeted deletion of the AMOG gene. These mice exhibit behaviourally normal development till postnatal day P16. At this time, they develop muscular weakness, incoordination, and tremor. Death invariably occurs 24-36 hours after onset of the symptoms. Histological and ultrastructural examination of brain sections show enlarged ventricles, brain edema, and swelling of astrocyte end feet. However, no disturbances of the architecture or cell migration in the brain can be detected. In order to identify long-term consequences of AMOG deficiency which might not yet be detectable at the time of death, we have established a CNS grafting model. The embryonal brain anlage (E10.5-E13.5) was grafted into the caudoputamen of wild type mice. The graft recipients are sacrificed up to 7 months after the procedure. Both wild type and AMOG deficient grafts develop and form solid neural tissue with neurons, myelinated axons, glial cells, and ventricular structures, as shown by histological and immunocytochemical analysis. However, no differences in grafts derived from wild type, heterozygous, and AMOG-deficient donors can be detected. Proliferation has been examined by BrdU immunocytochemistry. The blood-brain barrier as examined by repeated magnetic resonance imaging after injection of Gadolinium-DTPA has been shown to be largely reconstituted five weeks after grafting.

Adenosine Triphosphatases↗
PubMed1993

Functional characterization of beta isoforms of murine Na,K-ATPase. The adhesion molecule on glia (AMOG/beta 2), but not beta 1, promotes neurite outgrowth.

We have previously provided evidence for a dual function of the adhesion molecule on glia (AMOG/beta 2), the beta 2 subunit of the murine Na,K-ATPase, both as neural recognition molecule mediating neuron-glia interactions and as functional beta subunit of the sodium pump. To analyze the functional role of AMOG/beta 2 in neurite outgrowth, AMOG/beta 2-expressing L-cells were generated by transfection and used as substrates for neurite outgrowth of cerebellar and hippocampal neurons. AMOG/beta 2-transfected L-cells led to an increase in neurite length after 6 h, which was specifically inhibited by antibodies to AMOG/beta 2 and a neuronal membrane fraction. Moreover, the extracellular domain of AMOG/beta 2 generated as a soluble recombinant protein in Chinese hamster ovary cells partially inhibited the increase in neurite outgrowth on AMOG/beta 2-transfected L-cells. L-cells transfected with the mouse beta 1 subunit had no effect on neurite extension. Our observations show for the first time differences in functional properties for different beta isoforms of the Na,K-ATPase and suggest that AMOG/beta 2 but not beta 1 is able to interact with an unknown neuronal receptor leading to increased neurite outgrowth, most likely via signal transduction.

Adenosine Triphosphatases↗
PubMed1993

Myelin-associated glycoprotein is phosphorylated by protein kinase C.

The myelin-associated glycoprotein (MAG) is a neural recognition molecule involved in heterophilic interactions between myelin-forming cells and neurons. To characterize the molecular mechanisms underlying post-translational modifications which may be instrumental in signal transduction following the recognition event, we have studied the stimuli leading to modification of 32P-orthophosphate incorporation into MAG in cultures of oligodendrocytes or transformed differentiated Schwann cells. Here we show that in oligodendrocytes both the 67 and 72 kD isoforms of MAG were phosphorylated exclusively on serine, while in the transformed Schwann cells only the 67 kD isoform was found to be present and phosphorylated. The phorbol ester phorbol-12-myristoyl-13-acetate (PMA) did not affect biosynthesis of the protein backbone, but enhanced incorporation of phosphate by a factor of 2-3, indicating the involvement of protein kinase C. Exclusive phosphorylation of serine residues was also observed, when purified MAG was incubated with protein kinase C in the presence of [gamma-32P]ATP. In searching for the physiological stimuli which may trigger phosphorylation of MAG, cultures of oligodendrocytes were exposed to extracellular signals, such as coculture with dorsal root ganglion and spinal cord neurons carrying the MAG receptor, to membrane fractions of these neurons, monoclonal MAG antibody 513 binding to the recognition site of MAG, or platelet-derived growth factor. None of these additives modified the phosphorylation of MAG. These observations point to the possibility that phosphorylation of MAG is controlled by yet unknown intracellular cues rather than by extracellular signals interacting with cell surface receptors of oligodendrocytes.

Amino Acid Sequence↗
PubMed1993

Functional topography of the myelin-associated glycoprotein. I. Mapping of domains by electron microscopy.

The functional topography of the myelin-associated glycoprotein (MAG) was investigated by electron microscopic analysis of rotary-shadowed molecules of a MAG fragment (MAG 90) comprising the five immunoglobulin-like domains of the extracellular part of the molecule. MAG 90 molecules appeared as rod-like structures (18.5 +/- 1.2 nm long and 4.0 +/- 0.8 nm wide) with a globular domain at one end. Antibodies directed against the amino- and carboxy-terminus of MAG 90 interacted with the non-globular terminal region, indicating that the molecule is bent in the globular region with the amino- and carboxy-terminal arms in close apposition to each other. An antibody which interferes with the binding of MAG to neurons interacted predominantly with the globular domain of MAG 90. The fibril-forming collagen types I, III and V bound mainly to the non-globular terminal region of MAG 90, whereas the majority of heparin molecules interacted with the globular region of the molecule. The L2/HNK-1 carbohydrate structure was localized at the non-globular region in the protein fragment comprising the fourth and fifth immunoglobulin-like domains.

Animals↗
PubMed1993

Influence of janusin and tenascin on growth cone behavior in vitro.

Janusin and tenascin are glia-derived, structurally related, extracellular matrix glycoproteins of the J1 family that are expressed in vivo at times and in locations where active neurite outgrowth occurs, but also when the formation or stabilization of cytoarchitectonic boundaries appears to be in operation. To resolve this apparent functional dichotomy, we have studied the behavioral response of growth cones, growing in culture on the permissive substrate laminin to janusin and tenascin, by video time lapse microscopy. When janusin and tenascin were offered as sharp substrate boundaries, dorsal root ganglion (DRG) and retinal ganglion neuron growth cones avoided growing on these molecules, but were not induced to collapse. On the other hand, when janusin and tenascin were offered, in a mixture with laminin, as uniform substrates, DRG growth cones displayed a collapsed morphology and were able to advance at a faster rate than on laminin alone. In contrast, the outgrowth of retinal ganglion neuron growth cones was completely inhibited under these conditions, underscoring a cell type specificity in the response of growth cones to these molecules. Using several monoclonal antibodies binding to distinct epitopes on the tenascin molecule, we have identified two domains responsible for growth cone repulsion, on epidermal growth factor (EGF)-like repeats 3-5 and fibronectin type III homologous repeats 4 and 5. These domains are different from the one previously recognized to be involved in neurite outgrowth on a uniform tenascin substrate. We conclude that both molecules may promote or retard growth cone advance, depending on the spatial expression pattern and the neuronal cell type.

Animals↗
PubMed1993

The L2/HNK-1 carbohydrate mediates adhesion of neural cells to laminin.

The L2/HNK-1 carbohydrate epitope shared by several neural adhesion molecules has been implicated in cell-to-cell and cell-to-laminin adhesion (Keilhauer et al., Nature, 316, 728-730, 1985; Künemund et al., J. Cell Biol., 106, 213-223, 1988). As demonstrated previously for chicken retinal ganglion cells (Cole et al., Neurosci. Lett., 93, 170-175, 1988), cerebral cortex astrocytes or cerebellar neurons could not be shown to adhere to the substrate-bound L2/HNK-1 carbohydrate. The cell-bound L2/HNK-1 carbohydrate, however, was a potent mediator of astrocytic and neuronal cell adhesion to laminin, which was strongly reduced in the presence of the L2/HNK-1 carbohydrate-carrying glycolipids or Fab fragments of a monoclonal antibody against it. Inhibition of adhesion could not be observed in the presence of the negatively charged gangliosides or sulphatide, but in the presence of heparin. To investigate whether the L2/HNK-1 carbohydrate and heparin use the same or different binding sites on laminin, adhesion of cells to laminin was determined in the presence of heparin and Fab fragments of a monoclonal L2 antibody, which gave an additive value of inhibition as compared to the inhibition caused by the single compounds. This result, as well as studies of the binding of the L2/HNK-1 glycolipids to laminin in the presence of heparin, indicates that the L2/HNK-1 carbohydrate and heparin are implicated in different aspects of neural cell adhesion to laminin.

Animals↗
PubMed1993

L1 adhesion molecule on mouse leukocytes: regulation and involvement in endothelial cell binding.

L1 is a cell surface glycoprotein of the immunoglobulin superfamily which was initially shown to mediate adhesion between neural cells. Recently we have reported that L1 is expressed by bone marrow cells and the majority of mature lymphocytes (Kowitz et al., Eur. J. Immunol. 1992. 22: 1199-1205). To analyze the function of L1 on leukocytes we studied its regulation following cell activation. In vitro activation of B lymphocytes with lipopolysaccharide or T lymphocytes with phorbol 12-myristate 13-acetate/Ca2+ ionophore, concanavalin A or anti-CD3 monoclonal antibody as well as in vivo activation of V beta 8+ T cells with staphylococcal enterotoxin B (SEB) revealed a down-regulation of L1 within 48 h. A rapid loss of L1 expression was seen when mouse neutrophils were activated with PMA alone. This rapid loss paralleled the shedding of L-selectin. We also studied a possible role of L1 in the binding of leukocytes to endothelial cells. ESb-MP lymphoma cells with a high expression of L1 (L1hi) could bind to bend3 endothelioma cells without prior activation with inflammatory cytokines. The interaction was inhibited by anti-L1 antibodies. In contrast, ESb-MP cells with low L1 expression (L1lo) were only marginally bound. Latex beads coated with affinity-isolated L1 antigen were also able to bind to the endothelioma cells in a specific fashion. The binding of ESb-MP lymphoma cells required Ca2+ and Mg2+ ions and was sensitive to cold temperature. Since the endothelioma cells did not express L1 the binding mechanism studied here is distinct from the established L1-L1 homotypic interaction. It is possible that the novel L1-mediated adhesion pathway involves an unidentified ligand and could play a role in leukocyte migration.

Animals↗
PubMed1993

Lines of glial precursor cells immortalised with a temperature-sensitive oncogene give rise to astrocytes and oligodendrocytes following transplantation into demyelinated lesions in the central nervous system.

Immortalised lines of murine glial precursor cells expressing the neomycin resistance gene and a temperature-sensitive mutation of the SV 40 T oncogene were established from cultures of oligodendrocytes and precursor cells infected with a replication-incompetent, helper-free retrovirus. At the permissive temperature (33 degrees C), they could be continually propagated in vitro and cells were present expressing the 04 antigen specific for glial precursor cells and oligodendrocytes. At 38 degrees C, where the expression of the T antigen is down regulated, cell division largely ceased. During early passage in vitro, limited differentiation to a more mature phenotype, as evidenced by expression of GFAP and the oligodendrocyte marker 01 was observed at both 33 degrees C and 38 degrees C. When transplanted into demyelinating lesions in the spinal cords of adult rats early passages of the lines yielded myelin-forming oligodendrocytes and astrocytes. Cells from later passages of the lines although failing to synthesise myelin still associated specifically with the demyelinated axons. These experiments demonstrate the retention of physiological properties of these oncogene-carrying glial cells when transplanted in vivo and suggest that such immortalised populations can be used for the isolation of molecules regulating glial cell function.

Animals↗
PubMed1993

Expression of janusin (J1-160/180) in the retina and optic nerve of the developing and adult mouse.

We have analyzed the expression of the oligodendrocyte-derived extra-cellular matrix molecule janusin (previously termed J1-160/180) in the retina and optic nerve of developing and adult mice using indirect light and electron microscopic immunocytochemistry, immunoblot analysis, and enzyme-linked immunosorbent assay. In the optic nerve, janusin is not detectable in neonatal and only weakly detectable in 7-day-old animals. Expression is at a peak in 2- or 3-week-old animals and subsequently decreases with increasing age. In the retina, expression increases until the third postnatal week and then remains at a constant level. In immunocytochemical investigations at the light microscopic level, janusin was found in the myelinated regions of the nerve with spots of increased immunoreactivity possibly corresponding to an accumulation of the molecule at the nodes of Ranvier. At the electron microscopic level, contact sites between unmyelinated axons, between axons and glial cells, and between axons and processes of myelinating oligodendrocytes were immunoreactive. Cell surfaces of astrocytes at the periphery of the nerve and forming the glial-limiting membrane, in contrast, were only weakly immunopositive or negative. In cell cultures of young postnatal mouse or rat optic nerves, oligodendrocytes and type-2 astrocytes, but not type-1 astrocytes were stained by janusin antibodies. In the oligodendrocyte-free retina, janusin was detectable in association with neuronal cell surfaces, but not with cell surfaces of Müller cells or retinal astrocytes. Our observations indicate that expression of janusin in the optic nerve and in the retina is developmentally differentially regulated and that other cell types, in addition to oligodendrocytes, express the molecule. Since the time course of janusin expression in the optic nerve coincides with the appearance of oligodendrocytes and myelin and since janusin is associated with cell surfaces of oligodendrocytes and outer aspects of myelin sheaths and is concentrated at nodes of Ranvier, we suggest that janusin is functionally involved in the process of myelination.

Aging↗
PubMed1993

Astrocytes and neurons regulate the expression of the neural recognition molecule janusin by cultured oligodendrocytes.

Janusin (formerly designated J1-160/180) is an extracellular matrix glycoprotein highly homologous to tenascin, consisting of two major molecular forms of 160 and 180 kD expressed by oligodendrocytes and in myelin. Janusin expression is upregulated during myelination and in the adult it remains expressed at lower levels. It is also present at the node of Ranvier, where myelin, axon, and astrocytic process are in close contact. To gain an understanding of the regulatory mechanisms which may underlie expression of janusin, the differentiation stage-dependent expression of janusin was studied in cultures enriched in mouse oligodendrocytes and their precursor cells. Expression of janusin by these cells was highest on both A2B5+ and O4+/O1- oligodendroglial precursor cells and a subset of myelin associated glycoprotein-positive (MAG+) oligodendrocytes. Hardly any of the more differentiated O1+ or O10+ oligodendrocytes expressed janusin. Expression of janusin was influenced by co-culture with astrocytes or neurons. Astrocytes or astrocytic-conditioned culture supernatants elevated the expression of janusin by the more differentiated oligodendrocytes (O1+ or MAG+ cells), while its expression by oligodendroglial precursor cells was relatively unchanged. Platelet-derived growth factor, but not basic fibroblast growth factor, also elevated the expression of janusin by O1+ or O10+ oligodendrocytes. In contrast, co-culture with neurons originating from dorsal root ganglia or spinal cord decreased the expression of cell-bound janusin by oligodendrocytes and their precursor cells. These observations indicate that expression of janusin on these cells in culture is susceptible to opposing regulatory influences from astrocytes and neurons. Such influences may modulate the temporal and spatial distribution of janusin in the developing and adult central nervous system.

Animals↗
PubMed1993

Growth and degeneration of axons on astrocyte surfaces: effects on extracellular matrix and on later axonal growth.

Cultured astrocytes deposit an extracellular matrix which has been shown by immunocytochemistry to react with antibodies to tenascin, laminin, and fibronectin. Neuronal-glial interaction down-regulates these components of the matrix, causing a reduction in extracellular matrix localized to areas of contact with axons. Axons used for these experiments were from embryonic rat retinal explants. In some experiments explants were removed from the co-cultures and their axons allowed to degenerate. Degeneration of axons did not reverse the local reduction of extracellular matrix brought about by axon outgrowth. The period of axon outgrowth studied was 4-5 days; the period of degeneration was 2-3 days. Astrocytes alone, astrocytes with intact retinal explants, and astrocytes with 2-day degenerated retinal axons were tested for their ability to support neurite outgrowth from embryonic rat cortical neurons. Neurite outgrowth occurred on all astrocyte cultures. Cortical neurite lengths, measured 2 days after plating, were not significantly different between astrocytes alone and astrocytes with degenerated retinal axons. However, there was a tendency for neurites to be shorter on astrocytes with intact retinal axons present. Two conclusions may be drawn from these results. First, the state of differentiation of astrocytes, as marked by their assembly of extracellular matrix, is altered by contact with axons. Second, degeneration of axons alone, in the absence of other cell types, is not a sufficient signal to reestablish assembly of extracellular matrix. However, neither is it a sufficient signal to render astrocytes inhospitable to further axonal outgrowth or regeneration.

Animals↗
PubMed1993

Expression of L1 cell adhesion molecule is associated with lymphoma growth and metastasis.

The cell adhesion molecule (CAM) L1 is involved in homotypic and heterotypic adhesion between neural cells. It has recently also been identified on leucocytes. We have investigated the expression of L1 on hematopoietic tumor cell lines and found that several tumors including the ESb-MP lymphoma are positive for L1. A potential role for L1 in spontaneous metastasis formation was examined using these cells. From wild-type (wt) L1high lymphoma cells we selected by a fluorescence-activated cell sorter (FACS) stable L1low expression variants. Syngeneic DBA/2 mice injected subcutaneously with L1low clones showed faster primary tumor growth, developed visceral metastases significantly faster and died earlier than animals carrying L1high wt cells. L1 high revertants from the L1low variants showed again a reduced metastatic capacity and a malignancy similar to the wt cells. Expression of L1 on the tumor variants and revertants correlated directly with their homotypic aggregation behaviour in vitro. L1 expression correlated negatively with metastatic capacity. These results suggest that L1 molecules may contribute to the overall malignant potential of the lymphoma cells, presumably by interfering with cell-cell interactions critical for tumor growth and dissemination.

Animals↗
PubMed1993

Adaptation of a non-radioactive in situ hybridization method to electron microscopy: detection of tenascin mRNAs in mouse cerebellum with digoxigenin-labelled probes and gold-labelled antibodies.

In this study we describe a method for the detection of mRNAs at the ultrastructural level using a non-radioactive in situ hybridization method based on digoxigenin-labelled cRNA probes and gold-labelled digoxigenin-specific antibodies. We applied this protocol to an analysis of the expression of the extracellular matrix protein tenascin in the developing cerebellar cortex of the mouse. To gain an impression of the sensitivity attainable with digoxigenin-labelled probes, we first established at the light microscopic level that the hybridization signal obtained with the non-radioactive probe is as sensitive as that obtained with a 35S-labelled probe. The non-radioactive hybridization protocol was then combined with electron microscopic post-embedding and immunogold detection techniques. Tenascin-specific, digoxigenin-labelled cRNA probes were hybridized to ultrathin sections of Lowicryl K4M-embedded tissue and the probe/target mRNA hybrids were detected using gold-labelled antibodies to digoxigenin. In agreement with the observations from in situ hybridization at the light microscopic level, specific labelling was observed in Golgi epithelial cells in the region of the Purkinje cell layer and cells in the internal granular layer, which could be identified as astrocytes by ultrastructural criteria. Labelling was detectable in association with free ribosomes and ribosomes of the rough endoplasmic reticulum. In addition, focal hybridization signals were occasionally found in the nucleus. No signal was observed in Golgi epithelial cells or astrocytes using sense or in any other cerebellar cell type using either sense or anti-sense probes. The described in situ hybridization technique uses ultrastructural criteria to associate the presence of a given mRNA species with a particular cell type. Additionally, it provides information about the target mRNA's subcellular distribution, thus offering the possibility to study intracellular transport of particular mRNAs.

Acrylic Resins↗
PubMed1993

A role for the neural cell adhesion molecule in a late, consolidating phase of glycoprotein synthesis six hours following passive avoidance training of the young chick.

We have investigated the effect of intracranial injections of the amnestic anti-metabolite, 2-deoxygalactose, and antibodies to the neural cell adhesion molecule on retention of a one-trial passive avoidance task in chicks. Groups of chicks received bilateral intracranial injections of 10 mumol/hemisphere 2-deoxygalactose or 10 microliters/hemisphere anti-neural cell adhesion molecule and were tested 24 h following training. 2-Deoxygalactose injections were amnestic when administered at a previously established time (30 min pre-training). Here we show that the agent is also amnestic when injected within a second time window occurring specifically 6-8 h after training. Administration of 2-deoxygalactose between 2 and 6 h or after 8 h post-training was without effect on retention tested 24 h following training. Anti-neural cell adhesion molecule injections were amnestic only when performed at a time which coincided with the second phase of 2-deoxygalactose susceptibility. Further experiments demonstrated that the neural cell adhesion molecule is one of the molecules into which 2-deoxygalactose is incorporated. Additionally, we investigated the extent of diffusion of 2-deoxygalactose and anti-neural cell adhesion molecule following their injection, with respect to their residence in forebrain loci known to be involved in the memory for passive avoidance. We interpret these data as indicating that two waves of glycoprotein synthesis are necessary for the establishment of long-term memory for the experience of passive avoidance training. The evidence is discussed in the context of earlier results indicating that the two waves involve different glycoprotein species and, possibly, different forebrain regions. We speculate that the late phase of glycoprotein synthesis coincides with, and is required for, modulation of cell-cell adhesion processes, reflecting the selection and stabilization of synapses which maintain an enduring representation of long-term memory.

Analysis of Variance↗
PubMed1993

The F3/11 cell adhesion molecule mediates the repulsion of neurons by the extracellular matrix glycoprotein J1-160/180.

The oligodendrocyte-derived extracellular matrix protein J1-160/180 displays repellent substrate properties toward neurons. In a search for neuronal ligands mediating the response to J1-160/180, we have identified the F3/11 cell surface protein, a glyco-phosphatidylinositol-anchored member of the immunoglobulin superfamily. F3/11 mediates the initial recognition between a J1-160/180 substrate and cerebellar neurons or F3-transfected CHO cells. In cerebellar neurons, the F3/11-J1-160/180 interaction induces a repulsion consisting of the loss of substrate adhesion with time in culture and inhibition of neurite outgrowth. Antibody blocking experiments show that the avoidance response of neurites at J1-160/180 substrate borders is also mediated by F3/11. Active cell-cell and cell-substrate repulsion is considered a major mechanism governing the extent and directionality of axonal growth, but the ligand-receptor interactions involved have remained unknown. Our results show that F3/11 mediates the neuronal response to the repellent molecule J1-160/180 and may thus be involved in signal transduction leading to cell repulsion.

Animals↗