Elimination of aberrant DRG circuitries in Sema3A mutant mice leads to extensive neuronal deficits

PLoS One. 2013 Jul 26;8(7):e70085. doi: 10.1371/journal.pone.0070085. Print 2013.

Abstract

Axon guidance molecules determine the pattern of neuronal circuits. Accuracy of the process is ensured by unknown mechanisms that correct early guidance errors. Since the time frame of error correction in Sema3A null mice partly overlaps with the period of naturally occurring cell death in dorsal root ganglia (DRG) development, we tested the hypothesis that apoptosis of misguided neurons enables error correction. We crossed BAX null mice, in which DRG apoptosis is blocked, with Sema3A null mice to induce errors. Analyses of these double-null mouse embryos showed that the elimination of abnormal projections is not blocked in the absence of BAX. Surprisingly however, there are fewer surviving neurons in Sema3A null or Sema3A/BAX double-null newborn mice than in wild-type mice. These results suggest that guidance errors are corrected by a BAX-independent cell death mechanism. Thus, aberrant axonal guidance may lead to reductions in neuronal numbers to suboptimal levels, perhaps increasing the likelihood of neuropathological consequences later in life.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Survival
  • Ganglia, Spinal / cytology*
  • Ganglia, Spinal / embryology*
  • Gene Deletion
  • Mice
  • Mice, Knockout
  • Neurons / cytology
  • Neurons / metabolism
  • Semaphorin-3A / genetics*
  • bcl-2-Associated X Protein / genetics*

Substances

  • Semaphorin-3A
  • bcl-2-Associated X Protein

Grants and funding

This work was supported by a grant from the Israel Science Foundation (grant number 350/07), Legacy Heritage Biomedical Science Partnership (grant number 1306/10) (http://www.isf.org.il/) and the Ministry of Health (grant number 3000006210) (http://www.health.gov.il/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.