TY - JOUR
T1 - Semaphorin III is needed for normal patterning and growth of nerves, bones and heart
AU - Behar, O.
AU - Golden, J. A.
AU - Mashimo, H.
AU - Schoen, F. J.
AU - Fishman, M. C.
PY - 1996
Y1 - 1996
N2 - THE expression patterns of the recently discovered family of semaphorin genes suggests that they have widespread roles in embryonic development. Some seem to guide neuronal growth cones, but otherwise their functions are unknown. 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 heart. In vitro, semaphorin III causes growth-cone collapse, and repels cutaneous sensory axons from the ventral spinal cord. Mutants in the Drosophila gene semaII, which encodes a related semaphorin, die after eclosion, but no responsible abnormality is evident. 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.
AB - THE expression patterns of the recently discovered family of semaphorin genes suggests that they have widespread roles in embryonic development. Some seem to guide neuronal growth cones, but otherwise their functions are unknown. 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 heart. In vitro, semaphorin III causes growth-cone collapse, and repels cutaneous sensory axons from the ventral spinal cord. Mutants in the Drosophila gene semaII, which encodes a related semaphorin, die after eclosion, but no responsible abnormality is evident. 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.
UR - http://www.scopus.com/inward/record.url?scp=0029858256&partnerID=8YFLogxK
U2 - 10.1038/383525a0
DO - 10.1038/383525a0
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C2 - 8849723
AN - SCOPUS:0029858256
SN - 0028-0836
VL - 383
SP - 525
EP - 528
JO - Nature
JF - Nature
IS - 6600
ER -