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HMG-CoA reductase guides migrating primordial germ cells

Nature volume 396, pages 466–469 (1998)Cite this article

Abstract

The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is best known for catalysing a rate-limiting step in cholesterol biosynthesis, but it also participates in the production of a wide variety of other compounds1. Some clinical benefits attributed to inhibitors of HMG-CoA reductase are now thought to be independent of any serum cholesterol-lowering effect2,3. Here we describe a new cholesterol-independent role for HMG-CoA reductase, in regulating a developmental process: primordial germ cell migration. We show that in Drosophila this enzyme is highly expressed in the somatic gonad and that it is necessary for primordial germ cells to migrate to this tissue. Misexpression of HMG-CoA reductase is sufficient to attract primordial germ cells to tissues other than the gonadal mesoderm. We conclude that the regulated expression of HMG-CoA reductase has a critical developmental function in providing spatial information to guide migrating primordial germ cells.

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Figure 1: columbus is Drosophila HMG-CoA reductase.
Figure 2: The phenotype of hmgcrclb mutant embryos.
Figure 3: hmgcr is highly expressed in gonadal mesoderm.
Figure 4: Ectopic hmgcr expression is sufficient to attract PGCs to new locations.

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Acknowledgements

We thank D. Andrew, N. Bonini, N. Brown, B. Jones, R. Nusse, N. Perrimon, A.Williamson, the Bloomington Stock Center and the Berkeley Drosophila Genome Project for reagents; N. Perrimon, M. Petitt and S. Abmayr for sharing unpublished data; R. Brewster, S. Burden, G. Fishell, D.Littman, E. Skolnik and members of our laboratory for critically reading the manuscript; and M.Samuels for technical assistance. M.V.D. was supported by the American Cancer Society and the Howard Hughes Medical Institute; R.L. is an investigator of the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Department of Cell Biology, Developmental Genetics Program, Skirball Institute and Howard Hughes Medical Institute, New York University Medical Center, 540 First Avenue, New York, 10016, New York, USA

    Mark Van Doren, Heather Tarczy Broihier, Lisa A. Moore & Ruth Lehmann

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  1. Mark Van Doren
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  2. Heather Tarczy Broihier
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  3. Lisa A. Moore
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  4. Ruth Lehmann
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Correspondence to Ruth Lehmann.

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Van Doren, M., Broihier, H., Moore, L. et al. HMG-CoA reductase guides migrating primordial germ cells. Nature 396, 466–469 (1998). https://doi.org/10.1038/24871

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