A subpopulation of olfactory bulb GABAergic interneurons is derived from Emx1- and Dlx5/6-expressing progenitors

J Neurosci. 2007 Jun 27;27(26):6878-91. doi: 10.1523/JNEUROSCI.0254-07.2007.

Abstract

The subventricular zone (SVZ) of the postnatal brain continuously generates olfactory bulb (OB) interneurons. We show that calretinin+, calbindin+, and dopaminergic (TH+) periglomerular OB interneurons correspond to distinct subtypes of GABAergic cells; all were produced in the postnatal mouse brain, but they matured and were eliminated at different rates. The embryonic lateral ganglionic eminence (LGE) is thought to be the site of origin of postnatal SVZ neural progenitors. Consistently, grafts of the embryonic LGE into the adult brain SVZ generated many OB interneurons, including TH+ and calbindin+ periglomerular interneurons. However, calretinin+ cells were not produced from these LGE grafts. Surprisingly, pallial and septal embryonic progenitors transplanted into the adult brain SVZ also resulted in the generation of OB interneurons, including calretinin+ cells. A subset of Dlx2+ OB interneurons was derived from cells expressing Emx1, a transcription factor largely restricted to the pallium during development. Emx1 lineage-derived cells contributed a substantial portion of GABAergic cells in the OB, including calretinin+ interneurons. This is in contrast to cortex, in which Emx1 lineage-derived cells do not differentiate into GABAergic neurons. Our results suggest that some OB interneurons are derived from progenitors outside the LGE and that precursors expressing what has classically been considered a pallial transcription factor generate GABAergic interneurons.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Tissue Transplantation
  • Calbindin 2
  • Calbindins
  • Cell Differentiation / physiology
  • Cell Lineage / physiology
  • Cell Movement / physiology
  • Cells, Cultured
  • Dopamine / metabolism
  • Graft Survival / physiology
  • Homeodomain Proteins / metabolism*
  • Interneurons / cytology
  • Interneurons / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Olfactory Bulb / cytology
  • Olfactory Bulb / embryology*
  • Olfactory Bulb / metabolism
  • S100 Calcium Binding Protein G / metabolism
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Telencephalon / cytology
  • Telencephalon / embryology
  • Telencephalon / metabolism
  • Transcription Factors / metabolism*
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Calb2 protein, mouse
  • Calbindin 2
  • Calbindins
  • Distal-less homeobox proteins
  • Dlx5 protein, mouse
  • Dlx6 protein, mouse
  • Homeodomain Proteins
  • S100 Calcium Binding Protein G
  • Transcription Factors
  • empty spiracles homeobox proteins
  • gamma-Aminobutyric Acid
  • Dopamine