Multipotent peripheral glial cells generate neuroendocrine cells of the adrenal medulla

Science. 2017 Jul 7;357(6346):eaal3753. doi: 10.1126/science.aal3753.


Adrenaline is a fundamental circulating hormone for bodily responses to internal and external stressors. Chromaffin cells of the adrenal medulla (AM) represent the main neuroendocrine adrenergic component and are believed to differentiate from neural crest cells. We demonstrate that large numbers of chromaffin cells arise from peripheral glial stem cells, termed Schwann cell precursors (SCPs). SCPs migrate along the visceral motor nerve to the vicinity of the forming adrenal gland, where they detach from the nerve and form postsynaptic neuroendocrine chromaffin cells. An intricate molecular logic drives two sequential phases of gene expression, one unique for a distinct transient cellular state and another for cell type specification. Subsequently, these programs down-regulate SCP-gene and up-regulate chromaffin cell-gene networks. The AM forms through limited cell expansion and requires the recruitment of numerous SCPs. Thus, peripheral nerves serve as a stem cell niche for neuroendocrine system development.

Publication types

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

MeSH terms

  • Adrenal Medulla / cytology
  • Adrenal Medulla / embryology*
  • Animals
  • Cell Differentiation* / genetics
  • Cell Movement
  • Cell Proliferation
  • Chromaffin Cells / cytology*
  • Gene Expression Regulation, Developmental
  • Mice
  • Mice, Mutant Strains
  • Multipotent Stem Cells / cytology*
  • Myelin Proteolipid Protein / genetics
  • Neural Crest / cytology
  • Neural Stem Cells / cytology*
  • Neuroendocrine Cells / cytology*
  • Peripheral Nerves / cytology
  • SOXE Transcription Factors / genetics
  • Schwann Cells / cytology*
  • Stem Cell Niche / genetics
  • Transcription, Genetic


  • Myelin Proteolipid Protein
  • Plp1 protein, mouse
  • SOXE Transcription Factors
  • Sox10 protein, mouse