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Semaphorin III is needed for normal patterning and growth of nerves, bones and heart

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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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

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