Stereotyped pruning of long hippocampal axon branches triggered by retraction inducers of the semaphorin family.
Like naturally occurring neuronal cell death, stereotyped pruning of long axon branches to temporary targets is a widespread regressive phenomenon in the developing mammalian brain that helps sculpt the pattern of neuronal connections. The mechanisms controlling stereotyped pruning are, however, poorly understood. Here, we provide evidence that semaphorins, activating the Plexin-A3 receptor, function as retraction inducers to trigger-stereotyped pruning of specific hippocampal mossy fiber and pyramidal axon branches. Both pruning events are defective in Plexin-A3 mutants, reflecting a cell-autonomous requirement for Plexin-A3. The distribution of mRNAs for Sema3F and Sema3A makes them candidates for triggering the pruning. In vitro, hippocampal neurons respond to semaphorins by retracting axon branches. These results implicate semaphorins as retraction inducers controlling stereotyped pruning in the mammalian brain.
Department of Neurology, Program in Neuroscience, University of California-San Francisco, San Francisco, CA 94143, USA.
Anil
A
Bagri
Hwai-Jong
HJ
Cheng
Avraham
A
Yaron
Samuel J
SJ
Pleasure
Marc
M
Tessier-Lavigne
D000818:Animals; D017209:Apoptosis; D001369:Axons; D002455:Cell Division; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology*; D017403:In Situ Hybridization; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D039943:Neuropilin-2 / Q000235:genetics; D017966:Pyramidal Cells / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D039961:Semaphorins / Q000378:metabolism*; D015398:Signal Transduction
D009419:Nerve Tissue Proteins; D039943:Neuropilin-2; C492114:Plxna1 protein, mouse; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D039961:Semaphorins