Foxp2 Regulates Identities and Projection Patterns of Thalamic Nuclei During Development

Cereb Cortex. 2017 Jul 1;27(7):3648-3659. doi: 10.1093/cercor/bhw187.

Abstract

The molecular mechanisms underlying the formation of the thalamus during development have been investigated intensively. Although transcription factors distinguishing the thalamic primordium from adjacent brain structures have been uncovered, those involved in patterning inside the thalamus are largely unclear. Here, we show that Foxp2, a member of the forkhead transcription factor family, regulates thalamic patterning during development. We found a graded expression pattern of Foxp2 in the thalamic primordium of the mouse embryo. The expression levels of Foxp2 were high in the posterior region and low in the anterior region of the thalamic primordium. In Foxp2 (R552H) knockin mice, which have a missense loss-of-function mutation in the forkhead domain of Foxp2, thalamic nuclei of the posterior region of the thalamus were shrunken, while those of the intermediate region were expanded. Consistently, Foxp2 (R552H) knockin mice showed changes in thalamocortical projection patterns. Our results uncovered important roles of Foxp2 in thalamic patterning and thalamocortical projections during development.

Keywords: Foxp2; thalamic patterning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Body Patterning / genetics*
  • Calbindin 2 / metabolism
  • Deoxyribonucleases / metabolism
  • Electroporation / methods
  • Embryo, Mammalian
  • Gene Expression Regulation, Developmental / genetics*
  • Gene Expression Regulation, Developmental / physiology
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Hepatocyte Nuclear Factor 3-beta / genetics
  • Hepatocyte Nuclear Factor 3-beta / metabolism*
  • LIM-Homeodomain Proteins / metabolism
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mice
  • Mice, Inbred ICR
  • Mice, Transgenic
  • Mutation / genetics*
  • Neural Pathways / physiology*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Receptor, EphA8 / metabolism
  • Red Fluorescent Protein
  • Thalamic Nuclei* / embryology
  • Thalamic Nuclei* / growth & development
  • Thalamic Nuclei* / metabolism
  • Transcription Factors / metabolism
  • Vesicular Glutamate Transport Protein 2 / genetics
  • Vesicular Glutamate Transport Protein 2 / metabolism

Substances

  • Calbindin 2
  • Foxa2 protein, mouse
  • LIM-Homeodomain Proteins
  • Lhx2 protein, mouse
  • Luminescent Proteins
  • RNA, Small Interfering
  • Slc17a6 protein, mouse
  • Transcription Factors
  • Vesicular Glutamate Transport Protein 2
  • enhanced green fluorescent protein
  • Hepatocyte Nuclear Factor 3-beta
  • Green Fluorescent Proteins
  • Receptor, EphA8
  • Deoxyribonucleases
  • caspase-activated deoxyribonuclease