Netrins are diffusible chemotropic factors for commissural axons in the embryonic spinal cord

Kennedy, Timothy E.; Serafini, Tito; Torre, JoséR. de la; Tessier‐Lavigne, Marc

doi:10.1016/0092-8674(94)90421-9

Cited by 1,237 publications

(800 citation statements)

References 29 publications

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“…Consistent with their putative roles as diffusible signals, it was also shown that COS (immortalized monkey cell line) cells transfected with Netrin-1 or Netrin-2 cDNAs secrete the corresponding proteins into the medium and chemoattract commissural axons in vitro . Interestingly, while recombinant forms of both proteins have been shown to regulate commissural outgrowth in vitro, only netrin-1 mRNA expression is detected in the chick floor plate (netrin-2 is expressed in the ventral two-thirds of the spinal cord excluding the floor plate; Kennedy et al, 1994).…”

Section: Long-range Guidance To the Midline Vertebrate Spinal Cord: Nmentioning

confidence: 99%

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: Long-range Guidance To the Midline Vertebrate Spinal Cord: Nmentioning

confidence: 99%

Axon guidance at the midline choice point

Kaprielian

Runko

Imondi

2001

Developmental Dynamics

145

108

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“…The notochord, which originates from the node, acts as a secondary organizing region, controlling the induction and antero-posterior patterning of the neural plate, the induction of the floor plate in the midline of the neural plate and the dorsoventral patterning of somites (Fan & Tessier-Lavigne 1994; also for review see Smith (1994) and references therein). Finally, the floor plate produces signals required for dorso-ventral patterning of the neural tube and for axonal guidance (Tessier-Lavigne et al 1988;Yamada et al 1993;Kennedy et al 1994;Roelink et al 1995).…”

Section: Introductionmentioning

confidence: 99%

Enhancer analysis of the mouse HNF‐3β gene: regulatory elements for node/notochord and floor plate are independent and consist of multiple sub‐ elements

Sasaki

Hogan

1996

Genes to Cells

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“…36,37 Netrin-1 is the vertebrate homolog of UNC6, implying that it functions as a chemotrophic molecule that mediates axon outgrowth and orientation or neuronal migration during neuronal development. [38][39][40][41] It is encoded by the NTN1 gene and is a laminin-related, secreted protein, which has an amino (N)-terminal type IV laminin repeat (domain IV), followed by three cysteine-rich epidermal growth-factor modules (domains V1, V2 and V3), and a positively charged carboxy-terminal domain. 38 Another interesting observation was made in the p53-regulated UNC5B signaling pathway.…”

Section: P53 and Netrin-1mentioning

confidence: 99%

p53, apoptosis and axon-guidance molecules

Arakawa¹

2005

Cell Death Differ

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The p53 tumor-suppressor gene regulates apoptosis through the transcriptional activation of its target genes. The expression of the axon-guidance molecule UNC5B (also designated p53RDL1), which is a receptor for netrin-1, is directly regulated by p53. In the absence of netrin-1, UNC5B mediates p53-dependent apoptosis. Conversely, in the presence of netrin-1, p53-induced apoptosis is inhibited through the signaling pathway activated by the interaction between netrin-1 and UNC5B. A number of other molecules that are involved in axon guidance are inactivated in human cancers and are also regulated by p53. These findings suggest a close link between axon-guidance molecules and tumorigenesis.

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Netrins are diffusible chemotropic factors for commissural axons in the embryonic spinal cord

Cited by 1,237 publications

References 29 publications

Axon guidance at the midline choice point

Axon guidance at the midline choice point

Enhancer analysis of the mouse HNF‐3β gene: regulatory elements for node/notochord and floor plate are independent and consist of multiple sub‐ elements

p53, apoptosis and axon-guidance molecules

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