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Vol. 14, No. 17, pp. 2134-2139, September 1, 2000
1 Hormone Research Institute, Department of Medicine,
University of California-San Francisco, San Franscisco, California
94143 USA; 2 Center for Molecular Neurobiology, Hamburg,
Germany; 3 Nina Ireland Laboratory of Developmental
Neurobiology, University of California-San Francisco, San Francisco,
California 94143 USA; 4 Howard Hughes Medical Institute,
Department of Biochemistry and Molecular Biophysics, Center for
Neurobiology and Behavior, Columbia University, New York, New York
10032 USA; 5 Department of Cell and Molecular Biology, Medical
Nobel Institute, Karolinska Institute, S 17177 Stockholm, Sweden
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.
[Key Words: Nkx; spinal cord; motor neurons; neuronal specification; interneurons]
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