Ventral neural patterning by Nkx homeobox genes: Nkx6.1 controls somatic motor neuron and ventral interneuron fates
- Maike Sander1,2,6,
- Sussan Paydar3,6,
- Johan Ericson4,5,
- James Briscoe4,
- Elizabeth Berber3,
- Michael German1,
- Thomas M. Jessell4, and
- John L.R. Rubenstein3,7
- 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
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↵6 These authors contributed equally to this work.
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↵7 Corresponding author.
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E-MAIL jlrr{at}cgl.ucsf.edu; FAX (415) 502-7618.
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Article and publication are at www.genesdev.org/cgi/doi/10.1101/gad.820400.
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- Received May 18, 2000.
- Accepted July 11, 2000.
- Cold Spring Harbor Laboratory Press