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Neurogenomics

A new look at lipids in nerves

Once myelination starts, Schwann cells have been regarded as rather quiescent cells that live in a 'maintenance state' in the adult. But the results of a functional genomic analysis published in Genes and Development challenge this view by identifying a subset of genes that are selectively upregulated in adult peripheral nerves. The products of some of these genes are linked to lipid metabolism, and their discovery in this context might have profound implications for the understanding of certain types of peripheral neuropathy.

Verheijen et al. performed a microarray analysis of mouse sciatic nerves at different stages of development, from embryos to adult, and myelination, from pre- to postmyelinating. They identified 685 genes that were differentially expressed in these samples; some of these genes had been previously linked to forms of peripheral neuropathy, validating this approach for the identification of new disease-related candidate genes.

The authors went on to cluster the differentially expressed genes on the basis of their temporal expression patterns, and identified a group of 286 genes that was selectively upregulated in adult, postmyelinating nerves. After further sorting of the genes on the basis of their biological function, Verheijen et al. found that some were related to the metabolism of lipids. Although many of them were expressed by the epineurium, which is populated by adipocytes, several genes were expressed in the endoneurium, which largely consists of Schwann cells and axons. This group of genes included the transcription factors Srebp1 and Srebp2, which regulate the synthesis and uptake of cholesterol, and Lpin1, the product of which — the nuclear protein lipin-1 — is required for the proper development of adipose tissue. In fact, Verheijen et al. showed that mutations in Lpin1 lead to peripheral neuropathy, and to the dysregulation of genes that participate in lipid metabolism in nerves.

As we do not know the nature of the relevant genes in about half of the known forms of inherited neuropathy, the data of Verheijen et al. provide us with a valuable lead for their identification. Furthermore, the finding that alterations in lipid metabolism are associated with nerve damage should help us to understand peripheral neuropathies that are seen in conjunction with metabolic disorders such as diabetes.

References

ORIGINAL RESEARCH PAPER

  1. Verheijen, M. H. G. et al. Local regulation of fat metabolism in peripheral nerves. Genes Dev. 17, 2450–2464 (2003)

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FURTHER READING

  1. Suter, U. & Scherer, S. S. Disease mechanisms in inherited neuropathies. Nature Rev. Neurosci. 4, 714–726 (2003)

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López, J. A new look at lipids in nerves. Nat Rev Neurosci 4, 936 (2003). https://doi.org/10.1038/nrn1281

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  • DOI: https://doi.org/10.1038/nrn1281

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