title: EMX1 regulates NRP1-mediated wiring of the mouse anterior cingulate cortex.
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.
authors.affiliation: The University of Queensland, Queensland Brain Institute, Brisbane 4072, Australia.
authors.forename: Jonathan W C
authors.initials: JW
authors.lastname: Lim
authors.affiliation: The University of Queensland, Queensland Brain Institute, Brisbane 4072, Australia.
authors.forename: Amber-Lee S
authors.initials: AL
authors.lastname: Donahoo
authors.affiliation: The University of Queensland, Queensland Brain Institute, Brisbane 4072, Australia.
authors.forename: Jens
authors.initials: J
authors.lastname: Bunt
authors.affiliation: The University of Queensland, Queensland Brain Institute, Brisbane 4072, Australia.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Edwards
authors.affiliation: The University of Queensland, Queensland Brain Institute, Brisbane 4072, Australia.
authors.forename: Laura R
authors.initials: LR
authors.lastname: Fenlon
authors.affiliation: The University of Queensland, Queensland Brain Institute, Brisbane 4072, Australia.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: The University of Queensland, Queensland Brain Institute, Brisbane 4072, Australia.
authors.forename: Randal X
authors.initials: RX
authors.lastname: Moldrich
authors.affiliation: The University of Queensland, Queensland Brain Institute, Brisbane 4072, Australia The University of Queensland, The School of Biomedical Sciences, Brisbane 4072, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Piper
authors.affiliation: The University of Queensland, Queensland Brain Institute, Brisbane 4072, Australia.
authors.forename: Ilan
authors.initials: I
authors.lastname: Gobius
authors.affiliation: The University of Queensland, Institute for Molecular Bioscience, Brisbane 4072, Australia.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Bailey
authors.affiliation: The University of Queensland, Queensland Brain Institute, Brisbane 4072, Australia.
authors.forename: Naomi R
authors.initials: NR
authors.lastname: Wray
authors.affiliation: Wolfson Institute for Biomedical Research and Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Kessaris
authors.affiliation: Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Mu-Ming
authors.initials: MM
authors.lastname: Poo
authors.affiliation: Nina Ireland Laboratory of Developmental Neurobiology, University of California, San Francisco, San Francisco, CA 94143, USA Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: John L R
authors.initials: JL
authors.lastname: Rubenstein
authors.affiliation: The University of Queensland, Queensland Brain Institute, Brisbane 4072, Australia The University of Queensland, The School of Biomedical Sciences, Brisbane 4072, Australia richards@uq.edu.au.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Richards
mesh_terms: D061085:Agenesis of Corpus Callosum / Q000196:embryology / Q000235:genetics; D000818:Animals; D001369:Axons / Q000378:metabolism; D006179:Gyrus Cinguli / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039942:Neuropilin-1 / Q000378:metabolism*; D039961:Semaphorins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D000099260:Empty Spiracles Homeobox Proteins
chemical_list: D018398:Homeodomain Proteins; D039942:Neuropilin-1; D039961:Semaphorins; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins; C510203:semaphorin 3C protein, mouse
keywords: Anterograde tracing; Axon guidance; Cerebral cortex; Corpus callosum; In utero electroporation; Tractography