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Genetic ablation reveals that the roof plate is essential for dorsal interneuron specification

Nature volume 403, pages 734–740 (2000)Cite this article

Abstract

During neural development in vertebrates, a spatially ordered array of neurons is generated in response to inductive signals derived from localized organizing centres. One organizing centre that has been proposed to have a role in the control of neural patterning is the roof plate. To define the contribution of signals derived from the roof plate to the specification of neuronal cell types in the dorsal neural tube, we devised a genetic strategy to ablate the roof plate selectively in mouse embryos. Embryos without a roof plate lack all the interneuron subtypes that are normally generated in the dorsal third of the neural tube. Using a genetically based lineage analysis and in vitro assays, we show that the loss of these neurons results from the elimination of non-autonomous signals provided by the roof plate. These results reveal that the roof plate is essential for specifying multiple classes of neurons in the mammalian central nervous system.

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Figure 1: Conditional expression of a diphtheria toxin gene in roof-plate cells.
Figure 2: Initial steps of dorsal neural patterning occur normally in Gdf7–DTA embryos.
Figure 4: Loss of dorsal neural progenitors in Gdf7–DTA embryos.
Figure 3: Gdf7–DTA embryos lack roof-plate cells. In wild-type embryos examined at E11.5 (a–d), roof-plate cells express Gdf7 (a), Bmp6 (b), Msx1 (c) and Wnt1 (d).
Figure 5: Absence of dorsal interneuron classes in Gdf7–DTA embryos.
Figure 6: Lineage relationship between dorsal midline cells and D1B neurons.
Figure 7: Roof-plate rescue of dorsal neural progenitors and dorsal interneurons in Gdf7–DTA neural tissue.

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Acknowledgements

We thank A. Efstratiadis for the Hs–cre strain; B. Han and M. Mendelsohn for help with cell culture and generation of mouse strains; S. Kaplan for technical assistance; D. Anderson, J. Johnson, K. Kaestner, A. Pierani, P. Soriano and E. Turner for mouse strains and reagents; J. Millonig, K. Millen and M. E. Hatten for discussions; R. Axel, J. Briscoe, N. Shah and L. Vosshall for comments on the manuscript; and K. MacArthur for help in its preparation. K.J.L. was an HHMI Fellow of the Life Sciences Research Foundation. The work of P.D. was supported by an NIH grant to A. Efstratiadis. T.M.J. was supported by grants from the NIH and is an Investigator of the Howard Hughes Medical Institute.

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  1. Howard Hughes Medical Institute Department of Biochemistry and Molecular Biophysics, Centre for Neurobiology and Behavior,

    Kevin J. Lee & Thomas M. Jessell

  2. Department of Genetics and Development, Columbia University, New York, 10032, New York, USA

    Paula Dietrich

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Correspondence to Thomas M. Jessell.

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Lee, K., Dietrich, P. & Jessell, T. Genetic ablation reveals that the roof plate is essential for dorsal interneuron specification. Nature 403, 734–740 (2000). https://doi.org/10.1038/35001507

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