Gene targeting reveals a critical role for neurturin in the development and maintenance of enteric, sensory, and parasympathetic neurons

Neuron. 1999 Feb;22(2):253-63. doi: 10.1016/s0896-6273(00)81087-9.

Abstract

Neurturin (NTN) is a neuronal survival factor that activates the Ret tyrosine kinase in the presence of a GPI-linked coreceptor (either GFR alpha1 or GFR alpha2). Neurturin-deficient (NTN-/-) mice generated by homologous recombination are viable and fertile but have defects in the enteric nervous system, including reduced myenteric plexus innervation density and reduced gastrointestinal motility. Parasympathetic innervation of the lacrimal and submandibular salivary gland is dramatically reduced in NTN-/- mice, indicating that Neurturin is a neurotrophic factor for parasympathetic neurons. GFR alpha2-expressing cells in the trigeminal and dorsal root ganglia are also depleted in NTN-/- mice. The loss of GFR alpha2-expressing neurons, in conjunction with earlier studies, provides strong support for GFR alpha2/Ret receptor complexes as the critical mediators of NTN function in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Drosophila Proteins*
  • Gene Targeting
  • Glial Cell Line-Derived Neurotrophic Factor Receptors
  • Intestines / innervation*
  • Lacrimal Apparatus / innervation
  • Mice
  • Mice, Inbred Strains
  • Nerve Growth Factors / deficiency
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / physiology*
  • Neurons / physiology*
  • Neurons, Afferent / metabolism
  • Neurons, Afferent / physiology*
  • Neurturin
  • Parasympathetic Nervous System / cytology
  • Parasympathetic Nervous System / growth & development
  • Parasympathetic Nervous System / physiology*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Salivary Glands / innervation

Substances

  • Drosophila Proteins
  • Gfra2 protein, mouse
  • Glial Cell Line-Derived Neurotrophic Factor Receptors
  • Nerve Growth Factors
  • Neurturin
  • Nrtn protein, mouse
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases
  • Ret protein, Drosophila
  • Ret protein, mouse