EMX1 regulates NRP1-mediated wiring of the mouse anterior cingulate cortex

Jonathan W.C. Lim, Amber Lee S. Donahoo, Jens Bunt, Timothy J. Edwards, Laura R. Fenlon, Ying Liu, Jing Zhou, Randal X. Moldrich, Michael Piper, Ilan Gobius, Timothy L. Bailey, Naomi R. Wray, Nicoletta Kessaris, Mu Ming Poo, John L.R. Rubenstein, Linda J. Richards

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Transcription factors act during cortical development as master regulatory genes that specify cortical arealization and cellular identities. Although numerous transcription factors have been identified as being crucial for cortical development, little is known about their downstream targets and how they mediate the emergence of specific neuronal connections via selective axon guidance. The EMX transcription factors are essential for early patterning of the cerebral cortex, but whether EMX1 mediates interhemispheric connectivity by controlling corpus callosum formation remains unclear. Here, we demonstrate that in mice on the C57Bl/6 background EMX1 plays an essential role in the midline crossing of an axonal subpopulation of the corpus callosum derived from the anterior cingulate cortex. In the absence of EMX1, cingulate axons display reduced expression of the axon guidance receptor NRP1 and form aberrant axonal bundles within the rostral corpus callosum. EMX1 also functions as a transcriptional activator of Nrp1 expression in vitro, and overexpression of this protein in Emx1 knockout mice rescues the midline-crossing phenotype. These findings reveal a novel role for the EMX1 transcription factor in establishing cortical connectivity by regulating the interhemispheric wiring of a subpopulation of neurons within the mouse anterior cingulate cortex.

Original languageEnglish
Pages (from-to)3746-3757
Number of pages12
JournalDevelopment (Cambridge)
Volume142
Issue number21
DOIs
StatePublished - Nov 1 2015

Keywords

  • Anterograde tracing
  • Axon guidance
  • Cerebral cortex
  • Corpus callosum
  • In utero electroporation
  • Tractography

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