Biomedical subjects

Celine Plachez

Publications and source records attributed to Celine Plachez.

4 recordsLinked to original sources

PubMed2006

Imaging, anatomical, and molecular analysis of callosal formation in the developing human fetal brain.

A complex set of axonal guidance mechanisms are utilized by axons to locate and innervate their targets. In the developing mouse forebrain, we previously described several midline glial populations as well as various guidance molecules that regulate the formation of the corpus callosum. Since agenesis of the corpus callosum is associated with over 50 different human congenital syndromes, we wanted to investigate whether these same mechanisms also operate during human callosal development. Here we analyze midline glial and commissural development in human fetal brains ranging from 13 to 20 weeks of gestation using both diffusion tensor magnetic resonance imaging and immunohistochemistry. Through our combined radiological and histological studies, we demonstrate the morphological development of multiple forebrain commissures/decussations, including the corpus callosum, anterior commissure, hippocampal commissure, and the optic chiasm. Histological analyses demonstrated that all the midline glial populations previously described in mouse, as well as structures analogous to the subcallosal sling and cingulate pioneering axons, that mediate callosal axon guidance in mouse, are also present during human brain development. Finally, by Northern blot analysis, we have identified that molecules involved in mouse callosal development, including Slit, Robo, Netrin1, DCC, Nfia, Emx1, and GAP-43, are all expressed in human fetal brain. These data suggest that similar mechanisms and molecules required for midline commissure formation operate during both mouse and human brain development. Thus, the mouse is an excellent model system for studying normal and pathological commissural formation in human brain development.

Axons↗

PubMed2005

Mapping postnatal mouse brain development with diffusion tensor microimaging.

While mouse brain development has been extensively studied using histology, quantitative characterization of morphological changes is still a challenging task. This paper presents how developing brain structures can be quantitatively characterized with magnetic resonance diffusion tensor microimaging coupled with techniques of computational anatomy. High resolution diffusion tensor images of ex vivo postnatal mouse brains provide excellent contrasts to reveal the evolutions of mouse forebrain structures. Using anatomical landmarks defined on diffusion tensor images, tissue level growth patterns of mouse brains were quantified. The results demonstrate the use of these techniques to three-dimensionally and quantitatively characterize brain growth.

Algorithms↗

PubMed2005

Magnetic resonance diffusion tensor microimaging reveals a role for Bcl-x in brain development and homeostasis.

A new technique based on diffusion tensor imaging and computational neuroanatomy was developed to efficiently and quantitatively characterize the three-dimensional morphology of the developing brains. The technique was used to analyze the phenotype of conditional Bcl-x knock-out mice, in which the bcl-x gene was deleted specifically in neurons of the cerebral cortex and hippocampus beginning at embryonic day 13.5 as cells became postmitotic. Affected brain regions and associated axonal tracts showed severe atrophy in adult Bcl-x-deficient mice. Longitudinal studies revealed that these phenotypes are established by regressive processes that occur primarily during the first postnatal week, whereas neurogenesis and migration showed no obvious abnormality during embryonic stages. Specific families of white matter tracts that once formed normally during the embryonic stages underwent dramatic degeneration postnatally. Thus, this technique serves as a powerful tool to efficiently localize temporal and spatial manifestation of morphological phenotype.

Animals↗

PubMed2003

Abnormal development of forebrain midline glia and commissural projections in Nfia knock-out mice.

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.

Agenesis of Corpus Callosum↗