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

Amanda B. Wehner, Houari Abdesselem, Travis L. Dickendesher, Fumiyasu Imai, Yutaka Yoshida, Roman J. Giger, Brian A. Pierchala

Research output: Contribution to journalArticle

13 Citations (Scopus)


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 Sema3Ainitiated apoptotic signaling complex regulates the apoptosis of sympathetic neurons during the period of naturally occurring cell death.

Original languageEnglish
Pages (from-to)1560-1570
Number of pages11
JournalDevelopment (Cambridge)
Issue number9
Publication statusPublished - 1 May 2016



  • Cell death
  • Mouse
  • Rat
  • Sema3A
  • Sympathetic neurons

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Cite this

Wehner, A. B., Abdesselem, H., Dickendesher, T. L., Imai, F., Yoshida, Y., Giger, R. J., & Pierchala, B. A. (2016). Semaphorin 3A is a retrograde cell death signal in developing sympathetic neurons. Development (Cambridge), 143(9), 1560-1570.