Pax6 regulates Tbr1 and Tbr2 expressions in olfactory bulb mitral cells

Mol Cell Neurosci. 2013 May;54:58-70. doi: 10.1016/j.mcn.2013.01.002. Epub 2013 Jan 22.

Abstract

Tracking olfactory bulb mitral cell development with BrdU labeling, we find that mitral cells are generated from Pax6+ radial glial cells in the ventricular zone of the embryonic olfactory bulb. Unlike cortical projection neurons, postmitotic mitral cell precursors express both Tbr1 and Tbr2. Our tracking experiments revealed that down-regulation of Pax6 preceded up-regulation of Tbrs, and that Tbr1 emerged earlier than Tbr2. Using in utero electroporation, we also show that Pax6 negatively regulates the expression of Tbr1 and Tbr2 in postmitotic mitral cell precursors. Exogenous expression of Pax6 in embryonic olfactory bulb postmitotic precursors decreased the number of cells that progressed to a mitral cell fate. In contrast, exogenous expression of Pax6 resulted in an increase of GABAergic and/or dopaminergic interneurons. These results indicate that Pax6 is a regulator of fate determination of precursor cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Dopaminergic Neurons / cytology
  • Dopaminergic Neurons / metabolism
  • Eye Proteins / genetics*
  • Eye Proteins / metabolism
  • GABAergic Neurons / cytology
  • GABAergic Neurons / metabolism
  • Gene Expression Regulation, Developmental*
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Interneurons / cytology*
  • Interneurons / metabolism
  • Mice
  • Mitosis
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Neurogenesis
  • Neuroglia / cytology
  • Neuroglia / metabolism
  • Olfactory Bulb / cytology*
  • Olfactory Bulb / embryology
  • Olfactory Bulb / metabolism
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors / genetics*
  • Paired Box Transcription Factors / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • T-Box Domain Proteins / genetics*
  • T-Box Domain Proteins / metabolism

Substances

  • DNA-Binding Proteins
  • Eomes protein, mouse
  • Eye Proteins
  • Homeodomain Proteins
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Pax6 protein, mouse
  • Repressor Proteins
  • T-Box Domain Proteins
  • Tbr1 protein, mouse