Neural cadherin plays distinct roles for neuronal survival and axon growth under different regenerative conditions

Márcio Ribeiro, Konstantin Levay, Benito Yon, Ana C. Ayupe, Yadira Salgueiro, Kevin K. Park

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Growing axons in the CNS often migrate along specific pathways to reach their targets. During embryonic development, this migration is guided by different types of cell adhesion molecules (CAMs) present on the surface of glial cells or other neurons, including the neural cadherin (NCAD). Axons in the adult CNS can be stimulated to regenerate, and travel long distances. Crucially, however, while a few axons are guided effectively through the injured nerve under certain conditions, most axons never migrate properly. The molecular underpinnings of the variable growth, and the glial CAMs that are responsible for CNS axon regeneration remain unclear. Here we used optic nerve crush to demonstrate that NCAD plays multifaceted functions in facilitating CNS axon regeneration. Astrocyte-specific deletion of NCAD dramatically decreases regeneration induced by phosphatase and tensin homolog (PTEN) ablation in retinal ganglion cells (RGCs). Consistent with NCAD’s tendency to act as homodimers, deletion of NCAD in RGCs also reduces regeneration. Deletion of NCAD in astrocytes neither alters RGCs’ mammalian target of rapamycin complex 1 (mTORC1) activity nor lesion size, two factors known to affect regeneration. Unexpectedly, however, we find that NCAD deletion in RGCs reduces PTEN-deletion-induced RGC survival. We further show that NCAD deletion, in either astrocytes or RGCs, has negligible effects on the regeneration induced by ciliary neurotrophic factor (CNTF), suggesting that other CAMs are critical under this regenerative condition. Consistent with this notion, CNTF induces expression various integrins known to mediate cell adhesion. Together, our study reveals multilayered functions of NCAD and a molecular basis of variability in guided axon growth.

Original languageEnglish (US)
Article numberENEURO.0325-20.2020
Pages (from-to)1-18
Number of pages18
JournaleNeuro
Volume7
Issue number6
DOIs
StatePublished - 2020
Externally publishedYes

Keywords

  • Axon growth
  • Axon regeneration
  • Cadherins
  • NCAD
  • PTEN
  • Retinal ganglion cells

ASJC Scopus subject areas

  • Neuroscience(all)

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