The nuclear orphan receptor COUP-TFI is required for differentiation of subplate neurons and guidance of thalamocortical axons

Neuron. 1999 Dec;24(4):847-59. doi: 10.1016/s0896-6273(00)81032-6.


Chicken ovalbumin upstream promotor-transcription factor I (COUP-TFI), an orphan member of the nuclear receptor superfamily, is highly expressed in the developing nervous systems. In the cerebral cortex of Coup-tfl mutants, cortical layer IV was absent due to excessive cell death, a consequence of the failure of thalamocortical projections. Moreover, subplate neurons underwent improper differentiation and premature cell death during corticogenesis. Our results indicate that the subplate neuron defects lead to the failure of guidance and innervation of thalamocortical projections. Thus, our findings demonstrate a critical role of the subplate in early corticothalamic connectivity and confirm the importance of afferent innervation for the survival of layer IV neurons. These results also substantiate COUP-TFI as an important regulator of neuronal development and differentiation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antimetabolites
  • Axons / physiology
  • Bromodeoxyuridine
  • COUP Transcription Factor I
  • Carbocyanines
  • Cell Death / physiology
  • Cell Differentiation / physiology
  • Cerebral Cortex / cytology
  • Cerebral Cortex / growth & development
  • Cerebral Cortex / physiology*
  • DNA-Binding Proteins / physiology*
  • Fluorescent Dyes
  • Immunohistochemistry
  • In Situ Hybridization
  • Male
  • Mice
  • Mutation / genetics
  • Neural Pathways / growth & development
  • Neurons / physiology*
  • Receptors, Glucocorticoid / physiology*
  • Thalamus / cytology
  • Thalamus / growth & development
  • Thalamus / physiology*
  • Transcription Factors / physiology*


  • Antimetabolites
  • COUP Transcription Factor I
  • Carbocyanines
  • DNA-Binding Proteins
  • Fluorescent Dyes
  • Nr2f1 protein, mouse
  • Receptors, Glucocorticoid
  • Transcription Factors
  • 3,3'-dioctadecylindocarbocyanine
  • Bromodeoxyuridine