The COUP-TFII/Neuropilin-2 is a molecular switch steering diencephalon-derived GABAergic neurons in the developing mouse brain

Proc Natl Acad Sci U S A. 2015 Sep 8;112(36):E4985-94. doi: 10.1073/pnas.1420701112. Epub 2015 Aug 24.


The preoptic area (POa) of the rostral diencephalon supplies the neocortex and the amygdala with GABAergic neurons in the developing mouse brain. However, the molecular mechanisms that determine the pathway and destinations of POa-derived neurons have not yet been identified. Here we show that Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII)-induced expression of Neuropilin-2 (Nrp2) and its down-regulation control the destination of POa-derived GABAergic neurons. Initially, a majority of the POa-derived migrating neurons express COUP-TFII and form a caudal migratory stream toward the caudal subpallium. When a subpopulation of cells steers toward the neocortex, they exhibit decreased expression of COUP-TFII and Nrp2. The present findings show that suppression of COUP-TFII/Nrp2 changed the destination of the cells into the neocortex, whereas overexpression of COUP-TFII/Nrp2 caused cells to end up in the medial part of the amygdala. Taken together, these results reveal that COUP-TFII/Nrp2 is a molecular switch determining the pathway and destination of migrating GABAergic neurons born in the POa.

Keywords: COUP-TFII/Neuropilin-2; amygdala; caudal migratory stream; cortex; preoptic area.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / embryology
  • Amygdala / metabolism
  • Animals
  • Blotting, Western
  • Brain / embryology
  • Brain / metabolism*
  • COUP Transcription Factor II / genetics
  • COUP Transcription Factor II / metabolism*
  • Cell Movement / genetics
  • Diencephalon / embryology
  • Diencephalon / metabolism*
  • GABAergic Neurons / cytology
  • GABAergic Neurons / metabolism*
  • Gene Expression Regulation, Developmental
  • In Situ Hybridization
  • Mice, Inbred ICR
  • Mice, Knockout
  • Microscopy, Confocal
  • Neocortex / embryology
  • Neocortex / metabolism
  • Neuropilin-2 / genetics
  • Neuropilin-2 / metabolism*
  • Preoptic Area / embryology
  • Preoptic Area / metabolism
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Culture Techniques


  • COUP Transcription Factor II
  • Neuropilin-2