Clonally Related Forebrain Interneurons Disperse Broadly across Both Functional Areas and Structural Boundaries

Neuron. 2015 Sep 2;87(5):989-98. doi: 10.1016/j.neuron.2015.07.011. Epub 2015 Aug 20.

Abstract

The medial ganglionic eminence (MGE) gives rise to the majority of mouse forebrain interneurons. Here, we examine the lineage relationship among MGE-derived interneurons using a replication-defective retroviral library containing a highly diverse set of DNA barcodes. Recovering the barcodes from the mature progeny of infected progenitor cells enabled us to unambiguously determine their respective lineal relationship. We found that clonal dispersion occurs across large areas of the brain and is not restricted by anatomical divisions. As such, sibling interneurons can populate the cortex, hippocampus striatum, and globus pallidus. The majority of interneurons appeared to be generated from asymmetric divisions of MGE progenitor cells, followed by symmetric divisions within the subventricular zone. Altogether, our findings uncover that lineage relationships do not appear to determine interneuron allocation to particular regions. As such, it is likely that clonally related interneurons have considerable flexibility as to the particular forebrain circuits to which they can contribute.

Publication types

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

MeSH terms

  • 1-Alkyl-2-acetylglycerophosphocholine Esterase / genetics
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase / metabolism
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Differentiation / physiology
  • Cell Movement / physiology*
  • DNA Barcoding, Taxonomic
  • Embryo, Mammalian
  • Gene Expression Regulation, Developmental / physiology*
  • Gene Library
  • Geniculate Bodies / cytology*
  • Geniculate Bodies / embryology
  • Interneurons / physiology*
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Microdissection
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Nestin / genetics
  • Nestin / metabolism
  • Nuclear Proteins / genetics
  • Prosencephalon / cytology*
  • Prosencephalon / embryology
  • Stem Cells / physiology*
  • Thyroid Nuclear Factor 1
  • Time Factors
  • Transcription Factors / genetics

Substances

  • Carrier Proteins
  • Luminescent Proteins
  • Microtubule-Associated Proteins
  • Ndel1 protein, mouse
  • Nes protein, mouse
  • Nestin
  • Nuclear Proteins
  • Thyroid Nuclear Factor 1
  • Transcription Factors
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase
  • Pafah1b1 protein, mouse