Semaphorin III is needed for normal patterning and growth of nerves, bones and heart (original) (raw)
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- Published: 10 October 1996
Nature volume 383, pages 525–528 (1996)Cite this article
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Abstract
THE expression patterns of the recently discovered family of semaphorin genes suggests that they have widespread roles in embryonic development1–9. Some seem to guide neuronal growth cones, but otherwise their functions are unknown2,10–12. Semaphorin III is a membrane-associated secreted protein with a developmentally dynamic pattern of expression, including particular domains of the nervous system, the borders of developing bones, and the heart6,7. In vitro, semaphorin III causes growth-cone collapse, and repels cutaneous sensory axons from the ventral spinal cord2,11. Mutants in the Drosophila gene semaII, which encodes a related semaphorin, die after eclosion, but no responsible abnormality is evident3. We have generated mice mutant in the semaIII gene by homologous recombination. Here we show that in the mutants, some sensory axons project into inappropriate regions of the spinal cord where semaIII is normally expressed. The cerebral cortex of hymozygous mutant mice shows a paucity of neuropil and abnormally oriented neuronal processes, especially of the large pyramidal neurons. Certain embryonic bones and cartilaginous structures develop abnormally, with vertebral fusions and partial rib duplications. The few mice that survive more than a few days postnatally manifest pronounced and selective hypertrophy of the right ventricle of the heart and dilation of the right atrium. Thus, semaphorin III might serve as a signal that restrains growth in several developing organs.
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References
- Dodd, J. & Schuchardt, A. Cell 81, 471–474 (1995).
Article CAS Google Scholar - Luo, Y., Raible, D. & Raper, J. A. Cell 75, 217–227 (1993).
Article CAS Google Scholar - Kolodkin, A. L., Matthes, D. J. & Goodman, C. S. Cell 75, 1389–1399 (1993).
Article CAS Google Scholar - Luo, Y. et al. Neuron 14, 1131–1140 (1995).
Article CAS Google Scholar - Puschel, A. W., Adams, R. H. & Betz, H. Neuron 14, 941–948 (1995).
Article CAS Google Scholar - Wright, D. E., White, F. A., Gerfen, R. W., Silos-Santiago, I. & Snider, W. D. J. Comp. Neurol. 361, 321–333 (1995).
Article CAS Google Scholar - Shepherd, I., Luo, Y., Raper, J. A. & Chang, S. Dev. Biol. 173, 185–199 (1996).
Article CAS Google Scholar - Inagaki, S., Furuyama, T. & Iwahashi, Y. FEBS Lett. 370, 269–272 (1995).
Article CAS Google Scholar - Xiang, R. et al. Genomics 32, 39–48 (1996).
Article CAS Google Scholar - Kolodkin, A. L. et al. Neuron 9, 831–845 (1992).
Article CAS Google Scholar - Messersmith, E. K. et al. Neuron 14, 949–959 (1995).
Article CAS Google Scholar - Matthes, D. J., Sink, H., Kolodkin, A. L. & Goodman, C. S. Cell 81, 631–639 (1995).
Article CAS Google Scholar - Kolodkin, A. L. Trends Cell Biol. 6, 15–22 (1996).
Article CAS Google Scholar - Gibson, S. J. et al. J. Neurosci. 4, 3101–3111 (1984).
Article CAS Google Scholar - Mischel, P., Nyguyen, L. & Vinters, H. J. Neuropathol. Exp. Neurol. 54, 137–153 (1995).
Article CAS Google Scholar - Li, E., Beard, C., Forster, A. C., Bestor, T. H. & Jaenisch, R. Cold Spring Harb. Symp. Quant. Biol. LVIII, 297–305 (1993).
Article Google Scholar - Luo, G. et aL. Genes Dev. 9, 2808–2820 (1995).
Article CAS Google Scholar - Lyons, G. E. Trends Cardiovasc. Med. 4, 70–77 (1994).
Article CAS Google Scholar - Li, E., Bestor, T. H. & Jaenisch, R. Cell 69, 915–926 (1992).
Article CAS Google Scholar - Huang, L. P., Dawson, M. T., Bredt, S. D., Snyder, H. S. & Fishman, C. M. Cell 75, 1273–1286 (1993).
Article CAS Google Scholar - Behar, O., Ovadia, H., Polakiewicz, R. D. & Rosen, H. Endrocrinology 134, 475–481 (1994).
Article CAS Google Scholar - Zhang, W., Behringer, R. & Olson, E. N. Genes Dev. 9, 1388–1399 (1995).
Article CAS Google Scholar
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Authors and Affiliations
- Cardiovascular Research Center, Massachusetts General Hospital (East), 149 13th Street, 4th Floor, Charlestown, Massachusetts, 02129
Oded Behar, Hiroshi Mashimo & Mark C. Fishman - Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts, 02115, USA
Oded Behar, Hiroshi Mashimo & Mark C. Fishman - Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts, 02115, USA
Jeffrey A. Golden & Frederick J. Schoen
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- Oded Behar
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Behar, O., Golden, J., Mashimo, H. et al. Semaphorin III is needed for normal patterning and growth of nerves, bones and heart.Nature 383, 525–528 (1996). https://doi.org/10.1038/383525a0
- Received: 28 May 1996
- Accepted: 14 August 1996
- Issue Date: 10 October 1996
- DOI: https://doi.org/10.1038/383525a0