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

Lim, Jonathan W. C., Donahoo, Amber-Lee S., Bunt, Jens, Edwards, Timothy J., Fenlon, Laura R., Liu, Ying, Zhou, Jing, Moldrich, Randal X., Piper, Michael, Gobius, Ilan, Bailey, Timothy L., Wray, Naomi R., Kessaris, Nicoletta, Poo, Mu-Ming, Rubenstein, John L. R. and Richards, Linda J. (2015) EMX1 regulates NRP1-mediated wiring of the mouse anterior cingulate cortex. Development, 142 21: 3746-3757. doi:10.1242/dev.119909

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Author Lim, Jonathan W. C.
Donahoo, Amber-Lee S.
Bunt, Jens
Edwards, Timothy J.
Fenlon, Laura R.
Liu, Ying
Zhou, Jing
Moldrich, Randal X.
Piper, Michael
Gobius, Ilan
Bailey, Timothy L.
Wray, Naomi R.
Kessaris, Nicoletta
Poo, Mu-Ming
Rubenstein, John L. R.
Richards, Linda J.
Title EMX1 regulates NRP1-mediated wiring of the mouse anterior cingulate cortex
Journal name Development   Check publisher's open access policy
ISSN 1477-9129
Publication date 2015-09-03
Year available 2015
Sub-type Article (original research)
DOI 10.1242/dev.119909
Open Access Status File (Publisher version)
Volume 142
Issue 21
Start page 3746
End page 3757
Total pages 12
Place of publication Cambridge, United Kingdom
Publisher The Company of Biologists
Language eng
Subject 1312 Molecular Biology
1309 Developmental Biology
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.
Formatted 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.
Keyword Anterograde tracing
Axon guidance
Cerebral cortex
Corpus callosum
In utero electroporation
Tractography
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID APP1043045
2011CBA00400
RO1NS34661
FT120100170
Institutional Status UQ

 
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Created: Mon, 09 Nov 2015, 23:52:05 EST by Dr Michael Piper on behalf of School of Biomedical Sciences