Id2 is required for specification of dopaminergic neurons during adult olfactory neurogenesis

J Neurosci. 2008 Dec 24;28(52):14074-86. doi: 10.1523/JNEUROSCI.3188-08.2008.

Abstract

Understanding the biology of adult neural stem cells has important implications for nervous system development and may contribute to our understanding of neurodegenerative disorders and their treatment. We have characterized the process of olfactory neurogenesis in adult mice lacking inhibitor of DNA binding 2(-/-) (Id2(-/-)). We found a diminished olfactory bulb containing reduced numbers of granular and periglomerular neurons with a distinct paucity of dopaminergic periglomerular neurons. While no deficiency of the stem cell compartment was detectable, migrating neuroblasts in Id2(-/-) mutant mice prematurely undergo astroglial differentiation within a disorganized rostral migratory stream. Further, when evaluated in vitro loss of Id2 results in decreased proliferation of neural progenitors and decreased expression of the Hes1 and Ascl1 (Mash1) transcription factors, known mediators of neuronal differentiation. These data support a novel role for sustained Id2 expression in migrating neural progenitors mediating olfactory dopaminergic neuronal differentiation in adult animals.

Publication types

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

MeSH terms

  • Adult Stem Cells / physiology
  • Animals
  • Animals, Newborn
  • Astrocytes / physiology
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Bromodeoxyuridine / metabolism
  • Cell Count / methods
  • Cell Differentiation / genetics
  • Cells, Cultured
  • Discrimination, Psychological / physiology
  • Dopamine / metabolism*
  • Gene Expression Regulation, Developmental / genetics
  • Glial Fibrillary Acidic Protein / metabolism
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Inhibitor of Differentiation Protein 2 / deficiency
  • Inhibitor of Differentiation Protein 2 / physiology*
  • Mice
  • Mice, Knockout
  • Neurogenesis / genetics*
  • Neurogenesis / physiology
  • Neurons / physiology*
  • Olfactory Bulb / cytology*
  • Olfactory Bulb / growth & development
  • Olfactory Pathways / cytology
  • Olfactory Pathways / physiology
  • Smell / genetics
  • Statistics, Nonparametric
  • Transcription Factor HES-1
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Ascl1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Glial Fibrillary Acidic Protein
  • Hes1 protein, mouse
  • Homeodomain Proteins
  • Idb2 protein, mouse
  • Inhibitor of Differentiation Protein 2
  • Transcription Factor HES-1
  • Tyrosine 3-Monooxygenase
  • Bromodeoxyuridine
  • Dopamine