BMPs as Mediators of Roof Plate Repulsion of Commissural Neurons

Augsburger, Adela; Schuchardt, Anita; Hoskins, Sally G.; Dodd, Jane; Butler, Samantha J.

doi:10.1016/s0896-6273(00)80827-2

Cited by 242 publications

(236 citation statements)

References 89 publications

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“…Additionally, roof plate explants derived from mice lacking BMP7 show a markedly decreased ability to deflect axons in vitro. A rapid and direct effect on commissural axon growth was demonstrated by the ability of BMP7 to promote the collapse of cultured commissural growth cones (Augsburger et al, 1999). Consistent with an in vivo role for BMP7, commissural axon pathfinding defects have apparently been observed in the spinal cords of BMP7 knockout mice (see Augsburger et al, 1999).…”

Section: Vertebrate Spinal Cord: Bone Morphogenetic Proteinsmentioning

confidence: 89%

“…The roof plateenriched expression of several chondroitin (Snow et al, 1991;Katoh-Semba et al, 1995;Engel et al, 1996;Katoh-Semba et al, 1998) and keratan (Cole and McCabe, 1991; sulfate proteoglycans which are capable of inhibiting neurite outgrowth in vitro, provides support for this hypothesis. More recently, it was demonstrated that the roof plate is capable of deflecting and reorienting Netrin-1-responsive commissural axons from E11 rat dorsal spinal cord explants (Augsburger et al, 1999). The ability of roof plate explants to deflect commissural axons from as far away as 100 m suggested that this repulsive activity was associated with a diffusible molecule secreted by roof plate cells.…”

Section: Vertebrate Spinal Cord: Bone Morphogenetic Proteinsmentioning

confidence: 99%

“…The ability of roof plate explants to deflect commissural axons from as far away as 100 m suggested that this repulsive activity was associated with a diffusible molecule secreted by roof plate cells. Importantly, the repellent activity was shown to be restricted to the roof plate and specific for commissural axons (Augsburger et al, 1999). By employing a candidate molecule approach, it was further demonstrated that BMP7, a member of the TGF␤ family of signaling molecules referred to as bone morphogenetic proteins (BMPs), mimics the repellent roof plate activity.…”

Section: Vertebrate Spinal Cord: Bone Morphogenetic Proteinsmentioning

confidence: 99%

“…By employing a candidate molecule approach, it was further demonstrated that BMP7, a member of the TGF␤ family of signaling molecules referred to as bone morphogenetic proteins (BMPs), mimics the repellent roof plate activity. While BMP6, BMP7, and Gdf7 (a member of a distinct group of BMPs; see Lee and Jessell, 1999) mRNA are each expressed within the roof plate at a time when commissural axons are initiating ventrally-directed growth, only recombinant BMP7 was shown to repel and reorient commissural axons as effectively as isolated roof plate explants (Augsburger et al, 1999). Importantly, both an antibody specific for BMP7 and a BMP antagonist were used to convincingly demonstrate that this secreted factor represents a major component of the roof plate-associated repellent activity.…”

Section: Vertebrate Spinal Cord: Bone Morphogenetic Proteinsmentioning

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. 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.…”

Section: Novel Midline Markersmentioning

confidence: 99%

See 4 more Smart Citations

Axon guidance at the midline choice point

Kaprielian

Runko

Imondi

2001

Developmental Dynamics

145

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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Section: Vertebrate Spinal Cord: Bone Morphogenetic Proteinsmentioning

confidence: 89%

Section: Vertebrate Spinal Cord: Bone Morphogenetic Proteinsmentioning

confidence: 99%

Section: Vertebrate Spinal Cord: Bone Morphogenetic Proteinsmentioning

confidence: 99%

Section: Vertebrate Spinal Cord: Bone Morphogenetic Proteinsmentioning

confidence: 99%

Section: Novel Midline Markersmentioning

confidence: 99%

See 3 more Smart Citations

Axon guidance at the midline choice point

Kaprielian

Runko

Imondi

2001

Developmental Dynamics

145

108

View full text Add to dashboard Cite

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Dissection and Culture of Embryonic Spinal Commissural Neurons

Moore

Kennedy

2008

CP Neuroscience

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Studies of spinal commissural neurons have provided substantial insight into the mechanisms that regulate axon guidance. Explants of embryonic spinal cords and isolated spinal commissural neurons have been important experimental tools for the identification and characterization of several guidance cues, including netrins, semaphorins, slits, sonic hedgehog, BMPs, and wnts. In this unit, protocols are provided for establishing these explant assays to assess the outgrowth and turning capacity of commissural axons. In addition, methods are included for preparing cultures highly enriched with embryonic commissural neurons, which have been used to probe the biochemical signaling mechanisms regulating axon guidance.

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