Semaphorins 3A, 3C, and 3F in mesencephalic dopaminergic axon pathfinding.
By analyzing the mechanisms that govern dopaminergic axon pathfinding from the midbrain to the striatum in embryonic rat brains, we identified neuroepithelial regions that exert chemotropic effects on mesencephalic dopaminergic axons. Explants from the pretectum and the striatum showed an attractive effect, whereas those from the midhindbrain boundary, the dorsal thalamus, and the ventral thalamus had no effect. Expression of semaphorin (Sema) 3C and Sema3F in the pretectum and of Sema3A in the striatum suggested a role for these axon guidance molecules in dopaminergic axon pathfinding. When expressed in HEK293 cell aggregates, Sema3C had an attractive effect and enhanced axon growth, Sema3A enhanced axon growth, and Sema3F had a repulsive effect on dopaminergic axons. Antineuropilin-1 and antineuropilin-2 antibodies reduced attraction by the pretectum, whereas attraction by the striatum was not affected by the presence of antineuropilin-1 antibodies. Moreover, neuropilin-1- and neuropilin-2-soluble Fc chimeras reduced the attraction by the pretectum. These results suggest that semaphorins may help to establish the dopaminergic projection from the midbrain to the striatum during embryonic development.
Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico.
Hebert L
HL
Hernández-Montiel
Elisa
E
Tamariz
M Teresa
MT
Sandoval-Minero
Alfredo
A
Varela-Echavarría
D000818:Animals; D001369:Axons / Q000502:physiology*; D002478:Cells, Cultured; D004298:Dopamine / Q000502:physiology*; D005260:Female; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D008636:Mesencephalon / Q000166:cytology / Q000502:physiology*; D017072:Neostriatum / Q000166:cytology / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009434:Neural Pathways / Q000166:cytology / Q000254:growth & development; D039942:Neuropilin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D039943:Neuropilin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D040121:Semaphorin-3A / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013477:Superior Colliculi / Q000166:cytology / Q000502:physiology; D014162:Transfection
D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D039943:Neuropilin-2; C526853:Sema3C protein, rat; C506913:Sema3F protein, rat; C488218:Sema3a protein, rat; D040121:Semaphorin-3A; D039942:Neuropilin-1; D004298:Dopamine