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Development. 2016 May 1;143(9):1560-70. doi: 10.1242/dev.134627.

Semaphorin 3A is a retrograde cell death signal in developing sympathetic neurons.

Author information

1
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.
2
Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA.
3
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.
4
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45299, USA.
5
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.
6
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.

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.

KEYWORDS:

Cell death; Mouse; Rat; Sema3A; Sympathetic neurons

PMID:
27143756
PMCID:
PMC4909861
DOI:
10.1242/dev.134627
[Indexed for MEDLINE]
Free PMC Article

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