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Motor neuron columnar fate imposed by sequential phases of Hox-c activity

Nature volume 425, pages 926–933 (2003)Cite this article

Abstract

The organization of neurons into columns is a prominent feature of central nervous system structure and function. In many regions of the central nervous system the grouping of neurons into columns links cell-body position to axonal trajectory, thus contributing to the establishment of topographic neural maps. This link is prominent in the developing spinal cord, where columnar sets of motor neurons innervate distinct targets in the periphery. We show here that sequential phases of Hox-c protein expression and activity control the columnar differentiation of spinal motor neurons. Hox expression in neural progenitors is established by graded fibroblast growth factor signalling and translated into a distinct motor neuron Hox pattern. Motor neuron columnar fate then emerges through cell autonomous repressor and activator functions of Hox proteins. Hox proteins also direct the expression of genes that establish motor topographic projections, thus implicating Hox proteins as critical determinants of spinal motor neuron identity and organization.

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Figure 1: Hox-c protein expression and spinal motor neuron columnar identity.
Figure 2: Hox-c and motor column repatterning after FGF8 expression in brachial neural tube.
Figure 3: Motor columnar patterning activities of Hoxc9 and Hoxc6.
Figure 4: Rapid repatterning of neural progenitor Hox profile after brachial FGF8 expression.
Figure 5: Activities of Hoxc6 and Hoxc9 in post-mitotic neurons.
Figure 6: Actions of Engrailed repressor derivatives of Hoxc6 and Hoxc9 on columnar differentiation.
Figure 7: Hox6 and Hox9 activities in motor neuron columnar differentiation and topography.

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Acknowledgements

We thank F. Lo for technical assistance; C. Tabin for chick Hox in situ probes; and E. Laufer for advice and critical reagents. We thank R. Axel, J. DeNooij, J. Ericson, E. Laufer, R. Mann, B. Novitch and S. Wilson for comments, and K. MacArthur for help in preparing the manuscript. J.-P.L. is supported by a grant from NINDS and is a recipient of a Burroughs Wellcome Fund Career Award in Biomedical Sciences. J.D. is a research associate and T.M.J. an investigator of the Howard Hughes Medical Institute.

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  1. Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Center for Neurobiology and Behavior, Columbia University, 701 West 168th Street, New York, New York, 10032, USA

    Jeremy S. Dasen & Thomas M. Jessell

  2. Department of Neuroscience, University of Virginia School of Medicine, Lane Road extended, MR4, Room 5032, Charlottesville, Virginia, 22908, USA

    Jeh-Ping Liu

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Dasen, J., Liu, JP. & Jessell, T. Motor neuron columnar fate imposed by sequential phases of Hox-c activity. Nature 425, 926–933 (2003). https://doi.org/10.1038/nature02051

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