The dorsal aorta initiates a molecular cascade that instructs sympatho-adrenal specification

Science. 2012 Jun 22;336(6088):1578-81. doi: 10.1126/science.1222369.


The autonomic nervous system, which includes the sympathetic neurons and adrenal medulla, originates from the neural crest. Combining avian blood vessel-specific gene manipulation and mouse genetics, we addressed a long-standing question of how neural crest cells (NCCs) generate sympathetic and medullary lineages during embryogenesis. We found that the dorsal aorta acts as a morphogenetic signaling center that coordinates NCC migration and cell lineage segregation. Bone morphogenetic proteins (BMPs) produced by the dorsal aorta are critical for the production of the chemokine stromal cell-derived factor-1 (SDF -1) and Neuregulin 1 in the para-aortic region, which act as chemoattractants for early migration. Later, BMP signaling is directly involved in the sympatho-medullary segregation. This study provides insights into the complex developmental signaling cascade that instructs one of the earliest events of neurovascular interactions guiding embryonic development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex / embryology
  • Adrenal Cortex / metabolism
  • Adrenal Medulla / cytology*
  • Adrenal Medulla / embryology
  • Animals
  • Aorta / embryology*
  • Aorta / metabolism*
  • Avian Proteins / metabolism
  • Bone Morphogenetic Proteins / metabolism*
  • Cell Line
  • Cell Lineage
  • Cell Movement
  • Chemokine CXCL12 / metabolism
  • Chemotactic Factors / metabolism
  • Chick Embryo
  • Coculture Techniques
  • Embryonic Development
  • Ganglia, Sympathetic / cytology*
  • Mice
  • Mice, Knockout
  • Morphogenesis
  • Neural Crest / cytology*
  • Neural Crest / physiology
  • Neuregulin-1 / metabolism
  • Signal Transduction
  • Stem Cells / cytology
  • Stem Cells / physiology


  • Avian Proteins
  • Bone Morphogenetic Proteins
  • Chemokine CXCL12
  • Chemotactic Factors
  • NRG1 protein, Gallus gallus
  • Neuregulin-1
  • Nrg1 protein, mouse