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RET signaling is essential for migration, axonal growth and axon guidance of developing sympathetic neurons.


Sympathetic axons use blood vessels as an intermediate path to reach their final target tissues. The initial contact between differentiating sympathetic neurons and blood vessels occurs following the primary sympathetic chain formation, where precursors of sympathetic neurons migrate and project axons along or toward blood vessels. We demonstrate that, in Ret-deficient mice, neuronal precursors throughout the entire sympathetic nervous system fail to migrate and project axons properly. These primary deficits lead to mis-routing of sympathetic nerve trunks and accelerated cell death of sympathetic neurons later in development. Artemin is expressed in blood vessels during periods of early sympathetic differentiation, and can promote and attract axonal growth of the sympathetic ganglion in vitro. This analysis identifies RET and artemin as central regulators of early sympathetic innervation.

Pubmed ID: 11641220


  • Enomoto H
  • Crawford PA
  • Gorodinsky A
  • Heuckeroth RO
  • Johnson EM
  • Milbrandt J


Development (Cambridge, England)

Publication Data

October 19, 2001

Associated Grants

  • Agency: NICHD NIH HHS, Id: HD01487
  • Agency: NICHD NIH HHS, Id: KO8 HD01166-03
  • Agency: NIA NIH HHS, Id: R01 AG13730
  • Agency: NIDDK NIH HHS, Id: R01 DK57038-01
  • Agency: NINDS NIH HHS, Id: R01 NS39358

Mesh Terms

  • Animals
  • Axons
  • Cell Movement
  • Drosophila Proteins
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases
  • Signal Transduction
  • Sympathetic Nervous System