title: Semaphorin 3A is a retrograde cell death signal in developing sympathetic neurons.
abstract: During development of the peripheral nervous system, excess neurons are generated, most of which will be lost by programmed cell death due to a limited supply of neurotrophic factors from their targets. Other environmental factors, such as 'competition factors' produced by neurons themselves, and axon guidance molecules have also been implicated in developmental cell death. Semaphorin 3A (Sema3A), in addition to its function as a chemorepulsive guidance cue, can also induce death of sensory neurons in vitro The extent to which Sema3A regulates developmental cell death in vivo, however, is debated. We show that in compartmentalized cultures of rat sympathetic neurons, a Sema3A-initiated apoptosis signal is retrogradely transported from axon terminals to cell bodies to induce cell death. Sema3A-mediated apoptosis utilizes the extrinsic pathway and requires both neuropilin 1 and plexin A3. Sema3A is not retrogradely transported in older, survival factor-independent sympathetic neurons, and is much less effective at inducing apoptosis in these neurons. Importantly, deletion of either neuropilin 1 or plexin A3 significantly reduces developmental cell death in the superior cervical ganglia. Taken together, a Sema3A-initiated apoptotic signaling complex regulates the apoptosis of sympathetic neurons during the period of naturally occurring cell death.
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA Neuroscience Program, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Wehner
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA.
authors.forename: Houari
authors.initials: H
authors.lastname: Abdesselem
authors.affiliation: Neuroscience Program, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA Department of Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
authors.forename: Travis L
authors.initials: TL
authors.lastname: Dickendesher
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45299, USA.
authors.forename: Fumiyasu
authors.initials: F
authors.lastname: Imai
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45299, USA.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Neuroscience Program, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA Department of Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA Department of Neurology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
authors.forename: Roman J
authors.initials: RJ
authors.lastname: Giger
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA Neuroscience Program, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA pierchal@umich.edu.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Pierchala
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001369:Axons / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D040121:Semaphorin-3A / Q000378:metabolism*; D015398:Signal Transduction; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D013564:Sympathetic Nervous System / Q000196:embryology*
chemical_list: D009419:Nerve Tissue Proteins; C492111:Plxna3 protein, rat; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; C488218:Sema3a protein, rat; D040121:Semaphorin-3A; D039942:Neuropilin-1; D053148:Caspase 3
keywords: Cell death; Mouse; Rat; Sema3A; Sympathetic neurons