Expression of the repulsive guidance molecule RGM and its receptor neogenin after spinal cord injury in sea lamprey

Shifman, Michael I.; Yumul, Rae Eden; Laramore, Cindy; Selzer, Michael E.

doi:10.1016/j.expneurol.2009.02.011

Cited by 39 publications

(31 citation statements)

References 62 publications

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“…Nematode: UNC-6 (Ishii et al, 1992), UNC-40 (Chan et al, 1996), UNC-5 (Leung-Hagesteijn et al, 1992). Lamprey: netrin (Shifman and Selzer, 2000b), neogenin (Shifman et al, 2009), UNC-5 (Shifman and Selzer, 2000a). Leech: netrin (Gan et al, 1999).…”

Section: Reviewmentioning

confidence: 99%

Netrins: versatile extracellular cues with diverse functions

2011

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SummaryNetrins are secreted proteins that were first identified as guidance cues, directing cell and axon migration during neural development. Subsequent findings have demonstrated that netrins can influence the formation of multiple tissues, including the vasculature, lung, pancreas, muscle and mammary gland, by mediating cell migration, cell-cell interactions and cell-extracellular matrix adhesion. Recent evidence also implicates the ongoing expression of netrins and netrin receptors in the maintenance of cell-cell organisation in mature tissues. Here, we review the mechanisms involved in netrin signalling in vertebrate and invertebrate systems and discuss the functions of netrin signalling during the development of neural and non-neural tissues.Key words: DCC, Adhesion, Axon, Neogenin, Netrin, UNC5 IntroductionNetrins are a family of extracellular, laminin-related (see Glossary, Box 1) proteins that function as chemotropic guidance cues for migrating cells and axons during neural development. They act as chemoattractants for some cell types and chemorepellents for others. Loss-of-function mutations in netrin 1 or in certain netrin receptors are lethal in mice, highlighting the importance of netrin signalling during development. Insights into the functions of netrins have arisen from studies across a wide range of animal species, including invertebrates such as the nematode worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster, non-mammalian vertebrates such as the frog Xenopus laevis, and mammals including rats, mice and humans.Since its discovery in the early 1990s, it is now becoming clear that the netrin gene family exhibits a rich biology, with significance beyond neural development, and contributes to the organisation of multiple tissues. Along with a number of other identified axon guidance cues (Hinck, 2004), secreted netrins influence organogenesis outside the central nervous system (CNS), directing cell migration and mediating cell-cell adhesion in the lung, pancreas, mammary gland, vasculature and muscle (Kang et al., 2004; Lejmi et al., 2008;Liu et al., 2004;Lu et al., 2004;Srinivasan et al., 2003;Yebra et al., 2003). Here, we discuss the cell biology of netrin and netrin receptor functions and review the downstream signal transduction mechanisms that they activate. We also provide an overview of netrin function during development, both within the nervous system and within other developing organs and tissues. Netrin family membersThe first reported member of the netrin family, uncoordinated-6 (UNC-6), was identified in a search for gene products that regulate neural development in C. elegans (Ishii et al., 1992). Netrins have since been identified and studied in multiple vertebrate and invertebrate species (Table 1), including X. laevis (de la Torre et al., 1997), D. melanogaster (Harris et al., 1996;Mitchell et al., 1996) and the sea anemone Nematostella vectensis (Matus et al., 2006), an animal that exhibits early hallmarks of the origins of bilateral symmetry. In mammals, three...

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Section: Reviewmentioning

confidence: 99%

Netrins: versatile extracellular cues with diverse functions

2011

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“…Within the first 1–2 weeks after injury, the proximal portions of giant RS axons retract an average of 1–2 mm while the distal portion undergoes Wallerian degeneration (Roederer et al , 1983; Yin and Selzer, 1983; Zhang et al , 2005). At this time, activated microglia and macrophages accumulate, presumably via proliferation, as in other species (Shifman and Selzer, 2007; Shifman et al , 2009). By 3–4 weeks post-transection, giant RS axons begin to regenerate (Rovainen, 1976; Lurie et al , 1994).…”

Section: The Lamprey Spinal Cord Regenerates: An Experimental Opportumentioning

confidence: 89%

“…Ascending axons also regenerate in the proper direction (Yin and Selzer, 1983; Armstrong et al , 2003). Moreover, injury induces changes in the expression levels of several axon guidance molecules (Shifman and Selzer, 2000a, b, 2006, 2007; Shifman et al , 2009). Some of these guidance molecules, such as UNC5 and neogenin, are differentially expressed between good and bad regenerators, providing proof-of-concept for the identification of differences in gene expression between the two populations.…”

Section: The Lamprey Spinal Cord Regenerates: An Experimental Opportumentioning

confidence: 99%

Regeneration in the Era of Functional Genomics and Gene Network Analysis

Smith

Morgan

Zottoli

et al. 2011

The Biological Bulletin

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What gives an organism the ability to regrow tissues and to recover function where another organism fails is the central problem of regenerative biology. The challenge is to describe the mechanisms of regeneration at the molecular level, delivering detailed insights into the many components that are cross-regulated. In other words, a broad, yet deep dissection of the system-wide network of molecular interactions is needed. Functional genomics has been used to elucidate gene regulatory networks (GRNs) in developing tissues, which, like regeneration, are complex systems. Therefore, we reason that the GRN approach, aided by next generation technologies, can also be applied to study the molecular mechanisms underlying the complex functions of regeneration. We ask what characteristics a model system must have to support a GRN analysis. Our discussion focuses on regeneration in the central nervous system, where loss of function has particularly devastating consequences for an organism. We examine a cohort of cells conserved across all vertebrates, the reticulospinal (RS) neurons, which lend themselves well to experimental manipulations. In the lamprey, a jawless vertebrate, there are giant RS neurons whose large size and ability to regenerate make them particularly suited for a GRN analysis. Adding to their value, a distinct subset of lamprey RS neurons reproducibly fail to regenerate, presenting an opportunity for side-by-side comparison of gene networks that promote or inhibit regeneration. Thus, determining the GRN for regeneration in RS neurons will provide a mechanistic understanding of the fundamental cues that lead to success or failure to regenerate.

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“…Lamprey hematopoetic tissues include the typhlosole, a tissue that is analogous to bone marrow, as well as the gills, which are thymus-like (Bajoghli et al 2011). The lamprey CNS contains macrophages/microglia, as defined by their morphology and binding to isolectin-B4 (Shifman and Selzer, 2007; Shifman et al, 2009). While the source of lamprey microglia in the injured spinal cord is not well understood, there is evidence consistent with a peripheral origin (Laramore et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

“…Molecular constituents of the scar that are shared with or distinct from mammals are largely unknown in lamprey, although preliminary evidence suggests that CSPG does accumulate at the lesion, where they are detrimental to axon regeneration (Hu et al, 2013). As in mammals, lamprey microglia/macrophages are increased in number after SCI and subsets of microglia have been shown to express both axon guidance and repulsion molecules, weeks to months after injury (Laramore et al, 2011; Lau et al; Shifman and Selzer, 2007; Shifman et al, 2009). Application of cAMP to the spinal cord at the time of transection increased the numbers of microglia one-month post injury (Lau et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Non-mammalian model systems for studying neuro-immune interactions after spinal cord injury

Bloom¹

2014

Experimental Neurology

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Mammals exhibit poor recovery after injury to the spinal cord, where the loss of neurons and neuronal connections can be functionally devastating. In contrast, it has long been appreciated that many non-mammalian vertebrate species exhibit significant spontaneous functional recovery after spinal cord injury (SCI). Identifying the biological responses that support an organism's inability or ability to recover function after SCI is an important scientific and medical question. While recent advances have been made in understanding the responses to SCI in mammals, we remain without an effective clinical therapy for SCI. A comparative biological approach to understanding responses to SCI in non-mammalian vertebrates will yield important insights into mechanisms that promote recovery after SCI. Presently, mechanistic studies aimed at elucidating responses, both intrinsic and extrinsic to neurons, that result in different regenerative capacities after SCI across vertebrates are just in their early stages. There are several inhibitory mechanisms proposed to impede recovery from SCI in mammals, including reactive gliosis and scarring, myelin associated proteins, and a suboptimal immune response. One hypothesis to explain the robust regenerative capacity of several non-mammalian vertebrates is a lack of some or all of these inhibitory signals. This review presents the current knowledge of immune responses to SCI in several non-mammalian species that achieve anatomical and functional recovery after SCI. This subject is of growing interest, as studies increasingly show both beneficial and detrimental roles of the immune response following SCI in mammals. A long-term goal of biomedical research in all experimental models of SCI is to understand how to promote functional recovery after SCI in humans. Therefore, understanding immune responses to SCI in non-mammalian vertebrates that achieve functional recovery spontaneously may identify novel strategies to modulate immune responses in less regenerative species and promote recovery after SCI.

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Expression of the repulsive guidance molecule RGM and its receptor neogenin after spinal cord injury in sea lamprey

Cited by 39 publications

References 62 publications

Netrins: versatile extracellular cues with diverse functions

Netrins: versatile extracellular cues with diverse functions

Regeneration in the Era of Functional Genomics and Gene Network Analysis

Non-mammalian model systems for studying neuro-immune interactions after spinal cord injury

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