Identification of a Novel Neural Cell Adhesion Molecule-related Gene with a Potential Role in Selective Axonal Projection

Alenius, Mattias; Bohm, Staffan

doi:10.1074/jbc.272.42.26083

Cited by 92 publications

(63 citation statements)

References 25 publications

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“…It is an adhesion protein and in adults is expressed on the surface of specific neurons within the olfactory system and in other neural tissues, such as the retina (42,43). There are two isoforms of OCAM, a transmembrane form and a GPI-linked form, and both have the same extracellular domain structure as NCAM (42,43). In addition, there are consensus N-linked glycosylation sites on OCAM Ig5 in positions equivalent to those that are polysialylated on NCAM Ig5.…”

Section: Resultsmentioning

confidence: 99%

“…OCAM (42), also known as Rb-8 neural cell adhesion molecule (RNCAM) (44), NCAM2 (44), or mammalian fasciclin II (mamFasII) (45), was cloned by three groups in 1997 (42)(43)(44). It is an adhesion protein and in adults is expressed on the surface of specific neurons within the olfactory system and in other neural tissues, such as the retina (42,43). There are two isoforms of OCAM, a transmembrane form and a GPI-linked form, and both have the same extracellular domain structure as NCAM (42,43).…”

Section: Resultsmentioning

confidence: 99%

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Sequences from the First Fibronectin Type III Repeat of the Neural Cell Adhesion Molecule Allow O-Glycan Polysialylation of an Adhesion Molecule Chimera

Foley

Swartzentruber

Thompson

et al. 2010

Journal of Biological Chemistry

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Polysialic acid is a developmentally regulated, anti-adhesive polymer that is added to N-glycans on the fifth immunoglobulin domain (Ig5) of the neural cell adhesion molecule (NCAM). We found that the first fibronectin type III repeat (FN1) of NCAM is required for the polysialylation of N-glycans on the adjacent Ig5 domain, and we proposed that the polysialyltransferases recognize specific sequences in FN1 to position themselves for Ig5 N-glycan polysialylation. Other studies identified a novel FN1 acidic surface patch and ␣-helix that play roles in NCAM polysialylation. Here, we characterize the contribution of two additional FN1 sequences, Pro The neural cell adhesion molecule (NCAM)2 is a member of the immunoglobulin superfamily. It is expressed on the cell surface where it engages in homophilic and heterophilic interactions, resulting in cell adhesion and modulation of signal transduction cascades (reviewed in Refs. 1, 2). In the developing embryo and neonate, NCAM is modified by the addition of long chains of ␣2,8-polysialic acid (3, 4). The presence of this highly hydrated and negatively charged carbohydrate polymer disrupts overall cell adhesion and allows cell migration (5-7). Polysialylation is catalyzed by the polysialyltransferases (polySTs), . NCAM polysialylation is critical during embryogenesis and early postnatal development. Mice that are null for both polySTs are born at Mendelian ratios but have severe neuronal defects, fail to thrive, and the majority die within 4 weeks of birth (12). Simultaneous deletion of NCAM and the polySTs rescues the lethal phenotype, indicating that polysialic acid is required to down-regulate the adhesive properties of NCAM during development (12). In addition, using varying allelic combinations of ST8SiaIV, ST8SiaII, and NCAM, Hildebrandt et al. (13) demonstrated that an aberrant increase in the level of unpolysialylated NCAM caused defects in brain connectivity in postnatal day 1 mice.NCAM is mainly unpolysialylated in the adult brain (3, 4). However, polysialylated NCAM does persist in specific regions of the central nervous system, including the olfactory bulb and hippocampus, where it functions in cell migration, synaptic plasticity, and repair (14 -17). Highly polysialylated NCAM is also re-expressed in several cancers, including neuroblastoma, glioma, small cell and non-small cell lung tumors, and Wilms' tumor, where it has been suggested to promote cancer invasiveness (18 -23). Recently, polysialylated NCAM has been shown to enhance metastasis of a murine model of lung cancer (24) and has been implicated in colorectal carcinoma progression (25). In addition, polysialic acid has been demonstrated to be involved in hematopoietic development (26,27). For example, ST8SiaIV Ϫ/Ϫ mice have reduced thymocyte numbers due to fewer progenitor cells mobilizing to the thymus (27).Although NCAM is by far the most abundant and well documented polysialylated protein, it is striking that only six other polysialylated glycoproteins have been identified. These are the ␣ subu...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Sequences from the First Fibronectin Type III Repeat of the Neural Cell Adhesion Molecule Allow O-Glycan Polysialylation of an Adhesion Molecule Chimera

Foley

Swartzentruber

Thompson

et al. 2010

Journal of Biological Chemistry

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“…Robo-2 expression also partially overlaps regions of the OE containing OCAM-expressing OSNs that define zones II-IV of the OE (Fig. 1C,E) (Alenius and Bohm, 1997;Yoshihara et al, 1997). To further ask whether OSNs located in specific zones of the OE express robo-2, we compared its pattern of expression with the expression of specific OR in the adult OE.…”

Section: Robo-2 Expression By Olfactory Sensory Neuronsmentioning

confidence: 99%

Requirement for Slit-1 and Robo-2 in Zonal Segregation of Olfactory Sensory Neuron Axons in the Main Olfactory Bulb

Cho¹,

Lépine²,

Andrews³

et al. 2007

J. Neurosci.

111

125

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The formation of precise stereotypic connections in sensory systems is critical for the ability to detect and process signals from the environment. In the olfactory system, olfactory sensory neurons (OSNs) project axons to spatially defined glomeruli within the olfactory bulb (OB). A spatial relationship exists between the location of OSNs within the olfactory epithelium (OE) and their glomerular targets along the dorsoventral axis in the OB. The molecular mechanisms underlying the zonal segregation of OSN axons along the dorsoventral axis of the OB are poorly understood. Using robo-2 Ϫ/Ϫ (roundabout) and slit-1 Ϫ/Ϫ mice, we examined the role of the Slit family of axon guidance cues in the targeting of OSN axons during development. We show that a subset of OSN axons that normally project to the dorsal region of the OB mistarget and form glomeruli in the ventral region in robo-2 Ϫ/Ϫ and slit-1 Ϫ/Ϫ mice. In addition, we show that the Slit receptor, Robo-2, is expressed in OSNs in a high dorsomedial to low ventrolateral gradient across the OE and that Slit-1 and Slit-3 are expressed in the ventral region of the OB. These results indicate that the dorsal-to-ventral segregation of OSN axons are not solely defined by the location of OSNs within the OE but also relies on axon guidance cues.

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“…The mammalian olfactory epithelium displays a striking spatial organization, such that odorant receptors and other molecular markers are restricted to circumscribed zones that radiate along the dorsomedial-ventrolateral axis (Ressler et al, 1993;Vassar et al, 1993;Alenius and Bohm, 1997;Yoshihara et al, 1997;Norlin et al, 2001;Oka et al, 2003;Gussing and Bohm, 2004;Miyamichi et al, 2005;Tietjen et al, 2005). Dorsoventral organization within the olfactory epithelium plays an essential role in odorant receptor choice as well as in guiding topographic projections of ORN axons to the olfactory bulb (Miyamichi et al, 2005;Imai and Sakano, 2007).…”

Section: Regional Identity In the Olfactory Epitheliummentioning

confidence: 99%

Foxg1Is Required for Development of the Vertebrate Olfactory System

Duggan

DeMaria²,

Baudhuin³

et al. 2008

J. Neurosci.

107

102

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Illuminating the molecular identity and regulation of early progenitor cells in the olfactory sensory epithelium represents an important challenge in the field of neural development. We show in both mouse and zebrafish that the winged helix transcription factor Foxg1 is expressed in an early progenitor population of the olfactory placode. In the mouse, Foxg1 is first expressed throughout the olfactory placode but later becomes restricted to the ventrolateral olfactory epithelium. The essential role of Foxg1 in olfactory development is demonstrated by the strikingly severe phenotype of Foxg1 knock-out mice: older embryos have no recognizable olfactory structures, including epithelium, bulb, or vomeronasal organs. Initially, a small number of olfactory progenitors are specified but show defects in both proliferation and differentiation. Similarly, antisense RNA knockdown of Foxg1 expression in the zebrafish shows a reduction in the number of neurons and mitotic cells in olfactory rosettes, mirroring the phenotype seen in the mouse Foxg1 null mutant. Using mosaic analysis in the zebrafish, we show that Foxg1 is required cell-autonomously for the production of mature olfactory receptor neurons. Therefore, we identified an evolutionarily conserved requirement for Foxg1 in the development of the vertebrate olfactory system.

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Identification of a Novel Neural Cell Adhesion Molecule-related Gene with a Potential Role in Selective Axonal Projection

Cited by 92 publications

References 25 publications

Sequences from the First Fibronectin Type III Repeat of the Neural Cell Adhesion Molecule Allow O-Glycan Polysialylation of an Adhesion Molecule Chimera

Sequences from the First Fibronectin Type III Repeat of the Neural Cell Adhesion Molecule Allow O-Glycan Polysialylation of an Adhesion Molecule Chimera

Requirement for Slit-1 and Robo-2 in Zonal Segregation of Olfactory Sensory Neuron Axons in the Main Olfactory Bulb

Foxg1Is Required for Development of the Vertebrate Olfactory System

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