The Netrin family of guidance factors: emphasis on Netrin-1 signalling

Barallobre, Marı́a José; Pascual, Marta; Rı́o, José Antonio del; Soriano, Eduardo

doi:10.1016/j.brainresrev.2004.11.003

Cited by 183 publications

(149 citation statements)

References 261 publications

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“…Our findings suggest that netrin-1 may be involved in the AMPH-induced reorganization of VTA DA dendritic circuitry recently reported by Mueller et al (2006). Netrin-1 can attract and repel neurite processes depending on the receptors they express (Barallobre et al, 2005;Furrer et al, 2003;Manitt and Kennedy, 2002;Stein et al, 2001;Suli et al, 2006). Here, we show that both DCC and UNC-5 receptors are highly expressed by adult mesocorticolimbic DA neurons, and that these receptors are upregulated in the VTA by a mild AMPH treatment regimen similar to the one used by Mueller et al (2006).…”

supporting

confidence: 75%

Regulation of netrin-1 receptors by amphetamine in the adult brain

Yetnikoff¹,

Labelle‐Dumais²,

Flores³

2007

Neuroscience

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Netrin-1 is a guidance cue molecule fundamental to the organization of neuronal connectivity during development. Netrin-1 and its receptors, deleted in colorectal cancer (DCC) and UNC-5 homologues (UNC-5), continue to be expressed in the adult brain, although neither their function nor the kinds of events that activate their expression are known. Two lines of evidence suggest a role for netrin-1 in amphetamine-induced dopamine plasticity in the adult. First, DCC is highly expressed by adult dopamine neurons. Second, adult mice with reduced DCC levels do not develop amphetamine-induced behavioral sensitization. To explore the role of netrin-1 in amphetamine-induced plasticity, we examined the effects of sensitizing treatment regimens of amphetamine on DCC and/or UNC-5 protein expression in the adult rat. These treatments produced striking and enduring increases in DCC and UNC-5 expression in the cell body, but not terminal regions, of the mesocorticolimbic dopamine system. Notably, neuroadaptations in the cell body region of mesocorticolimbic dopamine neurons underlie the development of sensitization to the effects of amphetamine. Furthermore, these localized amphetamine-induced changes were prevented by co-treatment with an N-methyl-D-aspartate receptor antagonist, a treatment known to block the development of amphetamine-induced sensitization of behavioral activation, dopamine release and motivated behavior. Using immunohistochemistry, we showed that both DCC and UNC-5 receptors are highly expressed by adult mesocorticolimbic dopamine neurons. These results provide the first evidence that repeated exposure to a stimulant drug such as amphetamine affects netrin-1 receptor expression in the adult brain. Taken together, our findings suggest that changes in netrin-1 receptor expression may play a role in the lasting effects of exposure to amphetamine and other stimulant drugs. Keywords sensitization; DCC; UNC-5; plasticity; dopamine; glutamate Stimulant drugs, such as amphetamine, induce locomotor-activating and rewarding effects by increasing extracellular dopamine (DA) levels in striatal terminal regions. These behavioral and neurochemical effects become sensitized when the drug is administered repeatedly (Stewart and Badiani, 1993;Kalivas and Stewart, 1991;Vezina 2004). Key features of sensitization, including its gradual development and persistence over time, CIHR Author Manuscript CIHR Author Manuscript CIHR Author Manuscriptsuggest underlying alterations in the organization of mesocorticolimbic DA circuitry. Indeed, stimulant-induced modifications in dendritic structure have been identified in midbrain DA perikarya and in striatal and cortical DA terminal regions, suggesting alterations in patterns of synaptic connectivity within these regions (Berlanga et al., 2006;Kolb et al., 2003;Mueller et al., 2006; Kolb, 1997, 1999;Sarti et al., 2007). Although the mechanisms underlying amphetamine-induced plasticity of DA circuitry are unclear, it is known that the development of sensitization depends on (1) ...

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supporting

confidence: 75%

Regulation of netrin-1 receptors by amphetamine in the adult brain

Yetnikoff¹,

Labelle‐Dumais²,

Flores³

2007

Neuroscience

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“…It is possible that neogenin associates in a cis-manner with a variety of coreceptors in a context-dependent manner to provide appropriate signaling capabilities to receptor complexes. Interestingly, Unc5b is a netrin-1 receptor, both independently and as part of a complex with DCC, that modulates short-and long-distance axon repulsion (Barallobre et al, 2005;Round and Stein, 2007). It is likely, therefore, that the specific component composition of axon guidance receptor complexes regulates responses to multiple ligands in a spatiotemporal manner; this may serve as a paradigm for many types of receptor complexes during development in general, including neogenin:Cdo complexes.…”

Section: Discussionmentioning

confidence: 99%

Neogenin Regulates Skeletal Myofiber Size and Focal Adhesion Kinase and Extracellular Signal-regulated Kinase Activities In Vivo and In Vitro

Bae

Yang

Jiang

et al. 2009

MBoC

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A variety of signaling pathways participate in the development of skeletal muscle, but the extracellular cues that regulate such pathways in myofiber formation are not well understood. Neogenin is a receptor for ligands of the netrin and repulsive guidance molecule (RGM) families involved in axon guidance. We reported previously that neogenin promoted myotube formation by C2C12 myoblasts in vitro and that the related protein Cdo (also Cdon) was a potential neogenin coreceptor in myoblasts. We report here that mice homozygous for a gene-trap mutation in the Neo1 locus (encoding neogenin) develop myotomes normally but have small myofibers at embryonic day 18.5 and at 3 wk of age. Similarly, cultured myoblasts derived from such animals form smaller myotubes with fewer nuclei than myoblasts from control animals. These in vivo and in vitro defects are associated with low levels of the activated forms of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK), both known to be involved in myotube formation, and inefficient expression of certain muscle-specific proteins. Recombinant netrin-2 activates FAK and ERK in cultured myoblasts in a neogenin-and Cdo-dependent manner, whereas recombinant RGMc displays lesser ability to activate these kinases. Together, netrin-neogenin signaling is an important extracellular cue in regulation of myogenic differentiation and myofiber size. INTRODUCTIONSkeletal muscle is the most abundant tissue, by mass, in the vertebrate body. Muscles of the trunk and limbs arise from the somites, with myogenic progenitor cells derived from the dorsal region of the maturing somite, the dermomyotome (Tajbakhsh and Buckingham, 2000;Pownall et al., 2002;Charge and Rudnicki, 2004). In response to signals from the adjacent notochord, neural tube, and surface ectoderm, some dermomyotomal progenitors become committed to the muscle lineage and form the myotome, a set of differentiated muscle cells that underlies the dermomyotome. Subsequent embryonic, fetal, and postnatal stages of myogenesis are thought to involve additional muscle progenitors that migrate from the dermomyotome and ultimately establish the trunk and limb musculature, as well as satellite cells, adult muscle precursor cells (Gros et al., 2005;Kassar-Duchossoy et al., 2005;Relaix et al., 2005). Somitic progenitor cells are specified to become muscle lineage-committed myoblasts through the action of the myogenic basic helix-loop-helix transcription factors Myf5, MRF4, and MyoD, whereas differentiation of myoblasts is regulated by myogenin, MyoD, and MRF4 (Tajbakhsh, 2005). These and other transcription factors coordinate the process of differentiation, including cell cycle withdrawal, expression of muscle-specific proteins, cellular elongation, and fusion into multinucleated myofibers. Although transcriptional regulation is at the core of myogenesis, the formation and growth of myofibers is also controlled by a variety of signaling ligands and their receptors, including insulin-like growth factor-1, fibroblast growth fac...

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“…Similar to in vitro studies, the infected cells (neurons and astrocytes) expressed and secreted functional netrin-1 and acted on cells in brain tissue, including endothelial cells. Endogenous netrin-1, predominantly expressed by the floor plate cells in the central nervous system, induces axonal outgrowth, axonal orientation, and neuronal migration during neuronal development (Barallobre et al, 2005;Xie et al, 2006). Besides the aforementioned roles it plays in the central nervous system, NT-1 has also been implicated in regulating salivary gland migration (Kolesnikov and Beckendorf, 2005), regulating invasion and migration of mouse mammary epithelial cells (Strizzi et al, 2005), promoting lung branching morphogenesis (Liu et al, 2004), and mediating pancreatic epithelial cell adhesion (Hebrok and Reichardt, 2004).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Netrin-1 Induces Neovascularization in the Adult Mouse Brain

Fan

Shen

Chen

et al. 2008

J Cereb Blood Flow Metab

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Netrin-1 is a critical molecule for axonal pathfinding during embryo development, and because of its structural homology to the endothelial mitogens, it may share its effects on vascular network formation. Using an adeno-associated viral netrin-1 vector (AAV-NT-1) gene transfer, we demonstrated that netrin-1 was able to stimulate the proliferation and migration of human cerebral endothelial cells (HCECs) and human aortic smooth muscle cells (HASMCs) compared with the control (P < 0.05), and could also promote HCEC tube formation on matrigel (P < 0.05) in vitro. Moreover, netrin-1 hyperstimulation could promote focal neovascularization (P < 0.05) in the adult brain in vivo. Unlike VEGF-induced microvessel increase, netrin-1-induced newly formed vessels showed an artery-like phenotype, with an intact endothelial cell monolayer surrounded by multiple cell layers, including smooth muscle cells and an astrocyte-connected outer layer. Our findings suggest that netrin-1 plays an important role in promoting blood vessel formation in the adult rodent central nervous system, and could have broad implication in cerebrovascular development and remodeling.

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The Netrin family of guidance factors: emphasis on Netrin-1 signalling

Cited by 183 publications

References 261 publications

Regulation of netrin-1 receptors by amphetamine in the adult brain

Regulation of netrin-1 receptors by amphetamine in the adult brain

Neogenin Regulates Skeletal Myofiber Size and Focal Adhesion Kinase and Extracellular Signal-regulated Kinase Activities In Vivo and In Vitro

Overexpression of Netrin-1 Induces Neovascularization in the Adult Mouse Brain

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