Conditional ablation of Tbr2 results in abnormal development of the olfactory bulbs and subventricular zone-rostral migratory stream

Dev Dyn. 2014 Mar;243(3):440-50. doi: 10.1002/dvdy.24090. Epub 2013 Nov 29.

Abstract

Background: Development of the olfactory bulb (OB) is a complex process that requires contributions from several progenitor cell niches to generate neuronal diversity. Previous studies showed that Tbr2 is expressed during the generation of glutamatergic OB neurons in rodents. However, relatively little is known about the role of Tbr2 in the developing OB or in the subventricular zone-rostral migratory stream (SVZ-RMS) germinal niche that gives rise to many OB neurons.

Results: Here, we use conditional gene ablation strategies to knockout Tbr2 during embryonic mouse olfactory bulb morphogenesis, as well as during perinatal and adult neurogenesis from the SVZ-RMS niche, and describe the resulting phenotypes. We find that Tbr2 is important for the generation of mitral cells in the OB, and that the olfactory bulbs themselves are hypoplastic and disorganized in Tbr2 mutant mice. Furthermore, we show that the SVZ-RMS niche is expanded and disordered following loss of Tbr2, which leads to ectopic accumulation of neuroblasts in the RMS. Lastly, we show that adult glutamatergic neurogenesis from the SVZ is impaired by loss of Tbr2.

Conclusions: Tbr2 is essential for proper morphogenesis of the OB and SVZ-RMS, and is important for the generation of multiple lineages of glutamatergic olfactory bulb neurons.

Keywords: Tbr2; neural development; olfactory bulbs; rostral migratory stream; subventricular zone.

Publication types

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

MeSH terms

  • Animals
  • Gene Deletion
  • Mice
  • Mice, Mutant Strains
  • Morphogenesis / physiology*
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism*
  • Olfactory Bulb / cytology
  • Olfactory Bulb / embryology*
  • Olfactory Receptor Neurons / cytology
  • Olfactory Receptor Neurons / embryology*
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism*

Substances

  • Eomes protein, mouse
  • T-Box Domain Proteins