RT Journal Article SR Electronic T1 Abnormal Development of Forebrain Midline Glia and Commissural Projections in Nfia Knock-Out Mice JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 203 OP 212 DO 10.1523/JNEUROSCI.23-01-00203.2003 VO 23 IS 1 A1 Tianzhi Shu A1 Kenneth G. Butz A1 Celine Plachez A1 Richard M. Gronostajski A1 Linda J. Richards YR 2003 UL http://www.jneurosci.org/content/23/1/203.abstract AB Nuclear factor I (NFI) genes are expressed in multiple organs throughout development (Chaudhry et al., 1997; for review, seeGronostajski, 2000). All four NFI genes are expressed in embryonic mouse brain, with Nfia, Nfib, andNfix 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). BecauseNfia−/−mice show glial abnormalities and ACC, we asked whether defects in midline glial structures occur inNfia− / − mice. NFI-A protein is expressed in all three midline populations. InNfia− / − , 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.