The Netrin-1/DCC guidance system: dopamine pathway maturation and psychiatric disorders emerging in adolescence

Mol Psychiatry. 2020 Feb;25(2):297-307. doi: 10.1038/s41380-019-0561-7. Epub 2019 Oct 28.


Axon guidance molecules direct growing axons toward their targets, assembling the intricate wiring of the nervous system. One of these molecules, Netrin-1, and its receptor, DCC (deleted in colorectal cancer), has profound effects, in laboratory animals, on the adolescent expansion of mesocorticolimbic pathways, particularly dopamine. Now, a rapidly growing literature suggests that (1) these same alterations could occur in humans, and (2) genetic variants in Netrin-1 and DCC are associated with depression, schizophrenia, and substance use. Together, these findings provide compelling evidence that Netrin-1 and DCC influence mesocorticolimbic-related psychopathological states that emerge during adolescence.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adolescent
  • Axons / metabolism
  • Cells, Cultured
  • DCC Receptor / genetics*
  • DCC Receptor / metabolism
  • Dopamine / metabolism
  • Female
  • Humans
  • Male
  • Mental Disorders / genetics*
  • Mental Disorders / metabolism
  • Nerve Growth Factors / metabolism
  • Netrin-1 / genetics*
  • Netrin-1 / metabolism
  • Neurons / metabolism
  • Receptors, Cell Surface / genetics


  • DCC Receptor
  • DCC protein, human
  • NTN1 protein, human
  • Nerve Growth Factors
  • Receptors, Cell Surface
  • Netrin-1
  • Dopamine