title: Abnormal development of forebrain midline glia and commissural projections in Nfia knock-out mice.
abstract: Nuclear factor I (NFI) genes are expressed in multiple organs throughout development (Chaudhry et al., 1997; for review, see Gronostajski, 2000). All four NFI genes are expressed in embryonic mouse brain, with Nfia, Nfib, and Nfix being expressed highly in developing cortex (Chaudhry et al., 1997). Disruption of the Nfia gene causes agenesis of the corpus callosum (ACC), hydrocephalus, and reduced GFAP expression (das Neves et al., 1999). Three midline structures, the glial wedge, glia within the indusium griseum, and the glial sling are involved in development of the corpus callosum (Silver et al., 1982; Silver and Ogawa, 1983; Shu and Richards, 2001). Because Nfia(-)/- mice show glial abnormalities and ACC, we asked whether defects in midline glial structures occur in Nfia(-)/- mice. NFI-A protein is expressed in all three midline populations. In Nfia(-)/-, mice sling cells are generated but migrate abnormally into the septum and do not form a sling. Glia within the indusium griseum and the glial wedge are greatly reduced or absent and consequently Slit2 expression is also reduced. Although callosal axons approach the midline, they fail to cross and extend aberrantly into the septum. The hippocampal commissure is absent or reduced, whereas the ipsilaterally projecting perforating axons (Hankin and Silver, 1988; Shu et al., 2001) appear relatively normal. These results support an essential role for midline glia in callosum development and a role for Nfia in the formation of midline glial structures.
authors.affiliation: Department of Anatomy and Neurobiology, and the Program in Neuroscience, The University of Maryland, School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Tianzhi
authors.initials: T
authors.lastname: Shu
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Butz
authors.forename: Celine
authors.initials: C
authors.lastname: Plachez
authors.forename: Richard M
authors.initials: RM
authors.lastname: Gronostajski
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Richards
mesh_terms: D061085:Agenesis of Corpus Callosum; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000502:physiology; D003337:Corpus Callosum / Q000166:cytology / Q000196:embryology*; D004268:DNA-Binding Proteins; D006624:Hippocampus / Q000002:abnormalities / Q000166:cytology / Q000196:embryology; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051839:NFI Transcription Factors; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology*; D009687:Nuclear Proteins; D019580:Perforant Pathway; D016548:Prosencephalon / Q000002:abnormalities / Q000166:cytology / Q000196:embryology*; D011971:Receptors, Immunologic / Q000378:metabolism; D013687:Telencephalon / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D051839:NFI Transcription Factors; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011971:Receptors, Immunologic; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein; C497646:Nfia protein, mouse; C497650:Nfix protein, mouse; C070856:YBX1 protein, human