Neuropilin-2, a Novel Member of the Neuropilin Family, Is a High Affinity Receptor for the Semaphorins Sema E and Sema IV but Not Sema III

Chen, Hang; Chédotal, Alain; He, Zhigang; Goodman, Corey S.; Tessier‐Lavigne, Marc

doi:10.1016/s0896-6273(00)80371-2

Cited by 612 publications

(525 citation statements)

References 38 publications

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“…It is unlikely, given the low binding affinity of Sema3A for NPN2 (Chen et al, 1998) that this expression serves to separate these two cell populations. This finding may be the function of the low level of expression of Sema3F, the preferred ligand for NPN2 (Chen et al, 1997;Giger et al, 1998) in the arch periphery (Fig. 2P).…”

Section: Branchial Arch Expressionmentioning

confidence: 99%

“…Recent studies have demonstrated that Semas may also act as chemoattractants (Bagnard et al, 1998;de Castro et al, 1999;Polleux et al, 2000). A transmembrane protein, neuropilin-1 (NPN1) has been demonstrated to be a receptor for Sema3A Kolodkin et al, 1997) whereas the related molecule NPN2 was found to bind Sema3C and Sema3F (Chen et al, 1997(Chen et al, , 1998Giger et al, 1998). NPN1 forms a homodimeric receptor for Sema3A, NPN2 does likewise for Sema3F and they act in concert to form a heteromeric receptor for Sema3C (Chen et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

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Cranial expression of class 3 secreted semaphorins and their neuropilin receptors

Chilton

Guthrie

2003

Developmental Dynamics

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The semaphorin family of chemorepellents and their receptors the neuropilins are implicated in a variety of cellular processes, including axon guidance and cell migration. Semaphorins may bind more than one neuropilin or a heterodimer of both, thus a detailed knowledge of their expression patterns may reveal possible cases of redundancy or mutual antagonism. To assess their involvement in cranial development, we cloned fragments of the chick orthologues of Sema3B and Sema3F. We then carried out mRNA in situ hybridisation of all six class 3 semaphorins and both neuropilins in the embryonic chick head. We present evidence for spatiotemporal regulation of these molecules in the brainstem and developing head, including the eye, ear, and branchial arches. These expression patterns provide a basis for functional analysis of semaphorins and neuropilins in the development of axon projections and the morphogenesis of cranial structures. Developmental Dynamics 228:726 -733, 2003.

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Section: Branchial Arch Expressionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cranial expression of class 3 secreted semaphorins and their neuropilin receptors

Chilton

Guthrie

2003

Developmental Dynamics

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“…The spatiotemporal expression patterns of Slit-2, SEMA 3B and SEMA 3F in the embryonic mouse spinal cord suggest that Slit-2 and SEMA 3B are good candidates for mediating the repulsive activity associated with the floor plate, while SEMA 3F may account for the inhibitory activity associated with the ventral spinal cord (Zou et al, 2000). Interestingly, mice deficient in NPN-2, a high affinity receptor for SEMA 3B and SEMA 3F (Chen et al, 1997), exhibit pathfinding defects that are consistent with commissural axons encountering repulsive guidance cues in the floor plate and within the ventral spinal cord after they cross the midline (Zou et al, 2000). While the in vitro functional results provide strong support for commissural axons selectively gaining responsive to repellent guidance cues after crossing through the floor plate, a role for NPN-2 in mediating these responses is difficult to reconcile with the observation that NPN-2 protein is expressed on both uncrossed and crossed segments of commissural axons in vivo and in vitro (see Zou et al, 2000).…”

Section: Vertebrate Spinal Cordmentioning

confidence: 99%

“…These include Slit-1, Slit-2, Slit-3 (see Brose and TessierLavigne, 2000 and references therein), NPN-2 (Chen et al, 1997), B-class ephrins (Imondi et al, 2000), Annexin IV (Hamre et al, 1996), BMP-6 (see Lee et al, 2000), and VEMA (Runko et al, 1999). Given that the roof plate, like the floor plate, is thought to be an important source of guidance cues for extending axons (Snow et al, 1990;Augsburger et al, 1999), each of these proteins may play important roles in regulating the pathfinding of axons that grow near, or across, the dorsal midline of the spinal cord.…”

Section: Novel Midline Markersmentioning

confidence: 99%

“…Given that the roof plate, like the floor plate, is thought to be an important source of guidance cues for extending axons (Snow et al, 1990;Augsburger et al, 1999), each of these proteins may play important roles in regulating the pathfinding of axons that grow near, or across, the dorsal midline of the spinal cord. In fact, the Slits (Brose et al, 1999;Zou et al, 2000), Neuropilin-2 (Chen et al, 1997), B-class ephrins (Flanagan and Vanderhaeghen, 1998) and BMPs (Augsburger et al, 1999) have previously been shown to mediate repulsive axon guidance events in several neural systems. Thus, despite the fact that functions for Annexin IV and VEMA have yet to be established, it seems possible that their expression in both ventral and dorsal mid-line structures may be indicative of an important role in axon guidance.…”

Section: Novel Midline Markersmentioning

confidence: 99%

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Axon guidance at the midline choice point

Kaprielian

Runko

Imondi

2001

Developmental Dynamics

146

108

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The central nervous system (CNS) of higher organisms is bilaterally-symmetric. The transfer of information between the two sides of the nervous system occurs through commissures formed by neurons that project axons across the midline to the contralateral side of the CNS. Interestingly, these axons cross the midline only once. Other neurons extend axons that never cross the midline; they project exclusively on their own (ipsilateral) side of the CNS. Thus, the midline is an important choice point for several classes of pathfinding axons. Recent studies demonstrate that specialized midline cells play critical roles in regulating the guidance of both crossing and non-crossing axons at the ventral midline of the developing vertebrate spinal cord and the Drosophila ventral nerve cord. For example, these cells secrete attractive cues that guide commissural axons over long distances to the midline of the CNS. Furthermore, shortrange interactions between guidance cues present on the surfaces of midline cells, and their receptors expressed on the surfaces of pathfinding axons, allow commissural axons to cross the midline only once and prevent ipsilaterally-projecting axons from entering the midline. Remarkably, the molecular composition of commissural axon surfaces is dynamically-altered as they cross the midline. Consequently, commissural axons become responsive to repulsive midline guidance cues that they had previously ignored on the ipsilateral side of the midline. Concomitantly, commissural axons lose responsiveness to attractive guidance cues that had initially attracted them to the midline. Thus, these exquisitely regulated guidance systems prevent commissural axons from lingering within the confines of the midline and allow them to pioneer an appropriate pathway on the contralateral side of the CNS. Many aspects of midline guidance are controlled by mechanistically and evolutionarily-conserved ligand-receptor systems. Strikingly, recent studies demonstrate that these receptors are modular; the ectodomains determine ligand recognition and the cytoplasmic domains specify the response of an axon to a given guidance cue. Despite rapid and dramatic progress in elucidating the molecular mechanisms that control midline guidance, many questions remain.

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Comparison of neurotrophin and repellent sensitivities of early embryonic geniculate and trigeminal axons

et al. 2000

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Geniculate (gustatory) and trigeminal (somatosensory) afferents take different routes to the tongue during rat embryonic development. To learn more about the mechanisms controlling neurite outgrowth and axon guidance, we are studying the roles of diffusible factors. We previously profiled the in vitro sensitivity of trigeminal axons to neurotrophins and target-derived diffusible factors and now report on these properties for geniculate axons. GDNF, BDNF, and NT-4, but not NT-3 or NGF, stimulate geniculate axon outgrowth during the ages investigated, embryonic days 12-14. Sensitivity to effective neurotrophins is developmentally regulated and different from that of the trigeminal ganglion. In vitro coculture studies revealed that geniculate axons were repelled by branchial arch explants that were previously shown to be repellent to trigeminal axons (Rochlin and Farbman [1998] J Neurosci 18:6840-6852). In addition, some branchial arch explants and untransfected COS7 cells repelled geniculate but not trigeminal axons. Sema3A, a ligand for neuropilin-1, is effective in repelling geniculate and trigeminal axons, and antineuropilin-1, but not antineuropilin-2, completely blocks the repulsion by arch explants that repel axon outgrowth from both ganglia. Sema3A mRNA is concentrated in branchial arch epithelium at the appropriate time to mediate the repulsion. In Sema3A knockout mice, geniculate and trigeminal afferents explore medial regions of the immature tongue and surrounding territories not explored in heterozygotes, supporting our previous hypothesis that Sema3A-based repulsion mediates the early restriction of sensory afferents away from midline structures.

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Neuropilin-2, a Novel Member of the Neuropilin Family, Is a High Affinity Receptor for the Semaphorins Sema E and Sema IV but Not Sema III

Cited by 612 publications

References 38 publications

Cranial expression of class 3 secreted semaphorins and their neuropilin receptors

Cranial expression of class 3 secreted semaphorins and their neuropilin receptors

Axon guidance at the midline choice point

Comparison of neurotrophin and repellent sensitivities of early embryonic geniculate and trigeminal axons

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