Ventral neural patterning by Nkx homeobox genes: Nkx6.1 controls somatic motor neuron and ventral interneuron fates

  1. Maike Sander1,2,6,
  2. Sussan Paydar3,6,
  3. Johan Ericson4,5,
  4. James Briscoe4,
  5. Elizabeth Berber3,
  6. Michael German1,
  7. Thomas M. Jessell4, and
  8. John L.R. Rubenstein3,7
  1. 1Hormone Research Institute, Department of Medicine, University of California–San Francisco, San Franscisco, California 94143 USA; 2Center for Molecular Neurobiology, Hamburg, Germany; 3Nina Ireland Laboratory of Developmental Neurobiology, University of California–San Francisco, San Francisco, California 94143 USA; 4Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Center for Neurobiology and Behavior, Columbia University, New York, New York 10032 USA; 5Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, S 17177 Stockholm, Sweden

Abstract

There is growing evidence that sonic hedgehog (Shh) signaling regulates ventral neuronal fate in the vertebrate central nervous system through Nkx-class homeodomain proteins. We have examined the patterns of neurogenesis in mice carrying a targeted mutation in Nkx6.1. These mutants show a dorsal-to-ventral switch in the identity of progenitors and in the fate of postmitotic neurons. At many axial levels there is a complete block in the generation of V2 interneurons and motor neurons and a compensatory ventral expansion in the domain of generation of V1 neurons, demonstrating the essential functions of Nkx6.1 in regional patterning and neuronal fate determination.

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Footnotes

  • 6 These authors contributed equally to this work.

  • 7 Corresponding author.

  • E-MAIL jlrr{at}cgl.ucsf.edu; FAX (415) 502-7618.

  • Article and publication are at www.genesdev.org/cgi/doi/10.1101/gad.820400.

    • Received May 18, 2000.
    • Accepted July 11, 2000.
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