Altered distribution of dopaminergic neurons in the brain of L1 null mice

Brain Res Dev Brain Res. 2001 Jan 31;126(1):21-30. doi: 10.1016/s0165-3806(00)00129-2.

Abstract

Dopaminergic neurons of the mouse mesencephalon originate in the ventricular zone and migrate radially along radial glia then tangentially along nerve fibers that express the neural cell adhesion molecule L1 to form the substantia nigra (A9 group) and ventral tegmental area (VTA) (A10 group). The role of L1 in migration of dopaminergic neuronal precursors was investigated in L1 knockout mice by tyrosine hydroxylase (TH) immunostaining. An altered rostrocaudal distribution of dopaminergic neurons was observed within the substantia nigra and VTA of L1-minus mice. In L1-minus mice at postnatal day 0, TH-positive cells were present abnormally in the dorsomedial mesencephalon, suggesting impaired migration. Axons projecting from the substantia nigra to the caudate putamen also exhibited an abnormal targeting pattern. There was no evidence of dopaminergic cell loss in the mutant SN. Abnormal localization of dopaminergic neurons in L1-minus mice was also evident in the zona incerta of the thalamus (A13 group), and the arcuate (A12) and periventricular nucleus (A14) of the hypothalamus. Cell bodies and axons in the substantia nigra, VTA, and hypothalamus of wild type mouse embryos expressed L1. These results suggested that L1 plays an important developmental role in the organization of dopaminergic neuronal cell groups in the mesencephalon and diencephalon.

Publication types

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

MeSH terms

  • Animals
  • Cell Movement / physiology
  • Dopamine / physiology*
  • Female
  • Hypothalamus / cytology
  • Hypothalamus / immunology
  • In Situ Nick-End Labeling
  • Leukocyte L1 Antigen Complex
  • Male
  • Membrane Glycoproteins / genetics*
  • Mice
  • Mice, Knockout
  • Neural Cell Adhesion Molecules / genetics*
  • Neurons / cytology*
  • Neurons / enzymology
  • Substantia Nigra / cytology
  • Substantia Nigra / embryology
  • Tyrosine 3-Monooxygenase / analysis
  • Ventral Tegmental Area / cytology
  • Ventral Tegmental Area / embryology

Substances

  • Leukocyte L1 Antigen Complex
  • Membrane Glycoproteins
  • Neural Cell Adhesion Molecules
  • Tyrosine 3-Monooxygenase
  • Dopamine