Comprehensive and cell-type-based characterization of the dorsal midbrain during development

Genes Cells. 2019 Jan;24(1):41-59. doi: 10.1111/gtc.12656. Epub 2018 Dec 5.

Abstract

The layer structure has been intensively characterized in the developing neocortex and cerebellum based on the various molecular markers. However, as to the developing dorsal midbrain, comprehensive analyses have not been intensely carried out, and thus, the name as well as the definition of each layer is not commonly shared. Here, we redefined the three layers, such as the ventricular zone, intermediate zone and marginal zone, based on various markers for proliferation and differentiation in embryonic dorsal midbrain. Biphasic Ki67 expression defines the classical VZ, in which there is clear separation of the mitotic and interphase zones. Next, we mapped the distribution of immature neurons to the defined layers, based on markers for glutamatergic and GABAergic lineage. Interestingly, Tbr2 and Neurog2 were expressed in the postmitotic neurons. We also report that active (phosphorylated) JNK is a useful marker to demarcate layers during the embryonic stage. Finally, we validated the final arrival layers of the migratory glutamatergic and GABAergic neurons. These results form a foundation for analyses of brain development, especially in the proliferation and migration of excitatory and inhibitory neurons in the dorsal midbrain.

Keywords: Dorsal midbrain; Ki67; active JNK; layer classification.

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Differentiation
  • Cell Lineage
  • Cell Movement
  • Cell Proliferation
  • Embryonic Development*
  • Female
  • GABAergic Neurons / cytology
  • GABAergic Neurons / metabolism
  • Green Fluorescent Proteins / metabolism
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Mesencephalon / cytology*
  • Mesencephalon / embryology*
  • Mice, Inbred ICR
  • Mitosis
  • Nerve Tissue Proteins / metabolism
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Neurogenesis
  • Neurons / cytology
  • Neurons / metabolism
  • Transcription Factors / metabolism

Substances

  • Ascl1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Nerve Tissue Proteins
  • Neurog2 protein, mouse
  • Transcription Factors
  • Green Fluorescent Proteins
  • JNK Mitogen-Activated Protein Kinases