title: Nkx2.1-derived astrocytes and neurons together with Slit2 are indispensable for anterior commissure formation.
abstract: Guidepost cells present at and surrounding the midline provide guidance cues that orient the growing axons through commissures. Here we show that the transcription factor Nkx2.1 known to control the specification of GABAergic interneurons also regulates the differentiation of astroglia and polydendrocytes within the mouse anterior commissure (AC). Nkx2.1-positive glia were found to originate from three germinal regions of the ventral telencephalon. Nkx2.1-derived glia were observed in and around the AC region by E14.5. Thereafter, a selective cell ablation strategy showed a synergistic role of Nkx2.1-derived cells, both GABAergic interneurons and astroglia, towards the proper formation of the AC. Finally, our results reveal that the Nkx2.1-regulated cells mediate AC axon guidance through the expression of the repellent cue, Slit2. These results bring forth interesting insights about the spatial and temporal origin of midline telencephalic glia, and highlight the importance of neurons and astroglia towards the formation of midline commissures.
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, Lausanne CH-1005, Switzerland.
authors.forename: Shilpi
authors.initials: S
authors.lastname: Minocha
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, Lausanne CH-1005, Switzerland.
authors.forename: Delphine
authors.initials: D
authors.lastname: Valloton
authors.affiliation: 1] INSERM UMR-S968, Institut de la Vision, Paris F-75012, France [2] Sorbonne Université, UPMC University Paris 06, UMR_S 968, Institut de la Vision, Paris F-75012, France [3] CNRS, UMR_7210, Paris F-75012, France.
authors.forename: Athena R
authors.initials: AR
authors.lastname: Ypsilanti
authors.affiliation: Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal 23955, Saudi Arabia.
authors.forename: Hubert
authors.initials: H
authors.lastname: Fiumelli
authors.affiliation: EPFL, Station 19, Batiment-SV, Room SV-2816, Lausanne CH-1015, Switzerland.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Allen
authors.affiliation: Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine and Japan Science and Technology Agency, CREST, Maebashi 371-8511, Japan.
authors.forename: Yuchio
authors.initials: Y
authors.lastname: Yanagawa
authors.affiliation: Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas and Universidad Miguel Hernández, Sant Joan d'Alacant 03550, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Marin
authors.affiliation: 1] INSERM UMR-S968, Institut de la Vision, Paris F-75012, France [2] Sorbonne Université, UPMC University Paris 06, UMR_S 968, Institut de la Vision, Paris F-75012, France [3] CNRS, UMR_7210, Paris F-75012, France.
authors.forename: Alain
authors.identifier: 0000000175773794
authors.initials: A
authors.lastname: Chédotal
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, Lausanne CH-1005, Switzerland.
authors.forename: Jean-Pierre
authors.identifier: 0000000292297520
authors.initials: JP
authors.lastname: Hornung
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, Lausanne CH-1005, Switzerland.
authors.forename: Cécile
authors.initials: C
authors.lastname: Lebrand
mesh_terms: D000818:Animals; D066240:Anterior Commissure, Brain / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D001369:Axons; D002465:Cell Movement; D018274:Electroporation; D004622:Embryo, Mammalian; D059330:GABAergic Neurons / Q000166:cytology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D007395:Interneurons / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D013687:Telencephalon / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000378:metabolism*; D000098552:Slit Homolog 2 Protein
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D000098552:Slit Homolog 2 Protein