FACS-array Profiling of Striatal Projection Neuron Subtypes in Juvenile and Adult Mouse Brains

Nat Neurosci. 2006 Mar;9(3):443-52. doi: 10.1038/nn1654. Epub 2006 Feb 19.

Abstract

A major challenge in systems neuroscience is to perform precise molecular genetic analyses of a single neuronal population in the context of the complex mammalian brain. Existing technologies for profiling cell type-specific gene expression are largely limited to immature or morphologically identifiable neurons. In this study, we developed a simple method using fluorescent activated cell sorting (FACS) to purify genetically labeled neurons from juvenile and adult mouse brains for gene expression profiling. We identify and verify a new set of differentially expressed genes in the striatonigral and striatopallidal neurons, two functionally and clinically important projection neuron subtypes in the basal ganglia. We further demonstrate that Ebf1 is a lineage-specific transcription factor essential to the differentiation of striatonigral neurons. Our study provides a general approach for profiling cell type-specific gene expression in the mature mammalian brain and identifies a set of genes critical to the function and dysfunction of the striatal projection neuron circuit.

Publication types

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

MeSH terms

  • Aging / genetics
  • Animals
  • Cell Differentiation / genetics
  • Cell Lineage / genetics
  • DNA-Binding Proteins / genetics*
  • Flow Cytometry / methods*
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Developmental / genetics
  • Genetic Markers / genetics
  • Globus Pallidus / cytology
  • Globus Pallidus / growth & development
  • Globus Pallidus / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neostriatum / cytology*
  • Neostriatum / growth & development
  • Neostriatum / metabolism
  • Neural Pathways / cytology*
  • Neural Pathways / growth & development
  • Neural Pathways / metabolism
  • Neurons / cytology*
  • Neurons / metabolism
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Substantia Nigra / cytology
  • Substantia Nigra / growth & development
  • Substantia Nigra / metabolism
  • Trans-Activators / genetics*

Substances

  • DNA-Binding Proteins
  • Ebf1 protein, mouse
  • Genetic Markers
  • RNA, Messenger
  • Trans-Activators