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The mouse Dreher gene Lmx1a controls formation of the roof plate in the vertebrate CNS

Nature volume 403, pages 764–769 (2000)Cite this article

Abstract

In the vertebrate central nervous system (CNS), a cascade of signals that originates in the ectoderm adjacent to the neural tube is propagated by the roof plate to dorsalize the neural tube1. Here we report that the phenotype of the spontaneous neurological mutant mouse dreher ( dr)2,3,4,5 results from a failure of the roof plate to develop. Dorsalization of the neural tube is consequently affected: dorsal interneurons in the spinal cord and granule neurons in the cerebellar cortex are lost, and the dorsal vertebral neural arches fail to form. Positional cloning of dreher indicates that the LIM homeodomain protein, Lmx1a, is affected in three different alleles of dreher. Lmx1a is expressed in the roof plate along the neuraxis during development of the CNS. Thus, Lmx1a is required for development of the roof plate and, in turn, for specification of dorsal cell fates in the CNS and developing vertebrae.

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Figure 1: Postnatal brain phenotype.
Figure 2: Genetics.
Figure 3: Positional cloning.
Figure 4: drJ/drJ embryos lack a roof plate.
Figure 5: Spinal cord phenotype.
Figure 6: Cerebellar development.

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Acknowledgements

We thank D. Wahlsten for drsst embryos; J. Johnson for the Math1 in situ probe; T. Jessell for antibodies against LH2 and MafB; B. Hogan for the Bmp6 probe and E8.5 cDNA library. M. Cooper and D. Patterson provided technical assistance; C. Bonal and L. Chemes participated in the sequence analysis of drJ; N. Adams provided assistance with digital imaging; and D. Benyaklef prepared the Figures. We thank N. Heintz, T. Jessell, J. Alder, K. Lee, P. Matteson, R. Slavkov, R. Wingate and K. Zimmerman for helpful discussions. This work was supported by a Program Project grant (M.E.H.)

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Author notes

  1. James H. Millonig

    Present address: Center for Advanced Biotechnology and Medicine, Department of Neuroscience and Cell Biology, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, New Jersey, 08854-5638, USA

  2. James H. Millonig and Kathleen J. Millen: These authors contributed equally to this work

  3. Mary E. Hatten: Correspondence and requests for materials should be addressed to M.E.H. GenBank accession numbers for murine Lmx1a and EST AA881470 are AF226662 and AF226663 respectively.

Authors and Affiliations

  1. Laboratory of Developmental Neurobiology, The Rockefeller University , 1,230 York Avenue, New York, 10021-6399, New York , USA

    James H. Millonig & Kathleen J. Millen

  2. Center for Advanced Biotechnology and Medicine, Department of Neuroscience and Cell Biology, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, New Jersey, 08854-5638, USA

    Mary E. Hatten

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Correspondence to Mary E. Hatten.

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Millonig, J., Millen, K. & Hatten, M. The mouse Dreher gene Lmx1a controls formation of the roof plate in the vertebrate CNS. Nature 403, 764–769 (2000). https://doi.org/10.1038/35001573

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