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En passant neurotrophic action of an intermediate axonal target in the developing mammalian CNS

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Abstract

During development, neurons extend axons to their targets, then become dependent for their survival on trophic substances secreted by their target cells. Competition for limiting amounts of these substances is thought to account for much of the extensive naturally-occurring cell death that is seen throughout the nervous system. Here we show that spinal commissural neurons, a group of long projection neurons in the central nervous system (CNS), are also dependent for their survival on trophic support from one of their intermediate targets, the floor plate of the spinal cord. This dependence occurs during a several-day-long period when their axons extend along the floor plate, following which they develop additional trophic requirements. A dependence of neurons on trophic support derived en passant from their intermediate axonal targets provides a mechanism for rapidly eliminating misprojecting neurons, which may help to prevent the formation of aberrant neuronal circuits during the development of the nervous system.

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Figure 1: The floor plate (FP) secretes a diffusible factor(s) that suppresses the disintegration of commissural axons from E13 explants.
Figure 2: Axonal disintegration is associated with cell death within explants.
Figure 3: Developmental-stage dependence of axonal disintegration with or without FPCM.
Figure 4: Evidence for a decreasing ventral-to-dorsal gradient of floor-plate-derived trophic activity in the E13 spinal cord.
Figure 5: Local action of the floor plate-derived trophic activity on axons.
Figure 6: Commissural neurons acquire dependence on neurotrophins (NT) at a developmental stage equivalent to E17.

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Acknowledgements

We thank B. Barres for providing most of the factors tested, Amgen for the Steel Factor, D. Greenspan for BMP-1 protein, and R. O'Connor, J. Flanagan, M. W. Cowan, L. Reichardt, K. Brose, M. Galko and P. Leighton for helpful discussions and/or comments on the manuscript. Supported by a fellowship from the American Cancer Society to H.W. and by a grant from the National Institutes of Health to M.T.-L. M.T.-L. is an Investigator of the Howard Hughes Medical Institute.

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  1. Hao Wang

    Present address: Merck Research Labs, WP26-265, West Point, Pennsylvania, 19486, USA

  2. Marc Tessier-Lavigne: Correspondence and requests for materials should be addressed to M.T.-L.

Authors and Affiliations

  1. Departments of Anatomy and of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, 94143-0452, California, USA

    Hao Wang & Marc Tessier-Lavigne

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  1. Hao Wang
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Correspondence to Marc Tessier-Lavigne.

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Wang, H., Tessier-Lavigne, M. En passant neurotrophic action of an intermediate axonal target in the developing mammalian CNS. Nature 401, 765–769 (1999). https://doi.org/10.1038/44521

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