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TrkB receptor controls striatal formation by regulating the number of newborn striatal neurons

Academic Article
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Overview

authors

  • Baydyuk, M.
  • Russell, T.
  • Liao, G. Y.
  • Zang, K.
  • An, J. J.
  • Reichardt, L. F.
  • Xu, Baoji

publication date

  • January 2011

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • In the peripheral nervous system, target tissues control the final size of innervating neuronal populations by producing limited amounts of survival-promoting neurotrophic factors during development. However, it remains largely unknown if the same principle works to regulate the size of neuronal populations in the developing brain. Here we show that neurotrophin signaling mediated by the TrkB receptor controls striatal size by promoting the survival of developing medium-sized spiny neurons (MSNs). Selective deletion of the gene for the TrkB receptor in striatal progenitors, using the Dlx5/6-Cre transgene, led to a hindpaw-clasping phenotype and a 50% loss of MSNs without affecting striatal interneurons. This loss resulted mainly from increased apoptosis of newborn MSNs within their birthplace, the lateral ganglionic eminence. Among MSNs, those expressing the dopamine receptor D2 (DRD2) were most affected, as indicated by a drastic loss of these neurons and specific down-regulation of the DRD2 and enkephalin. This specific phenotype of mutant animals is likely due to preferential TrkB expression in DRD2 MSNs. These findings suggest that neurotrophins can control the size of neuronal populations in the brain by promoting the survival of newborn neurons before they migrate to their final destinations.

subject areas

  • Animals
  • Animals, Newborn
  • Apoptosis
  • Brain-Derived Neurotrophic Factor
  • Cell Count
  • Corpus Striatum
  • Down-Regulation
  • Enkephalins
  • Female
  • Homeodomain Proteins
  • Immunoblotting
  • Immunohistochemistry
  • In Situ Hybridization
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Neurons
  • Receptor, trkB
  • Receptors, Dopamine D2
  • Time Factors
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Research

keywords

  • brain-derived neurotrophic factor
  • cell death
  • dopamine receptor D1a
  • striatum
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Identity

PubMed Central ID

  • PMC3029684

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.1004744108

PubMed ID

  • 21205893
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Additional Document Info

start page

  • 1669

end page

  • 1674

volume

  • 108

issue

  • 4

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