In Drosophila, the glial cell missing gene (Gcm 1) directs one of the central steps in the differentiation of neuroepithelial cells into neurons, astrocytes, oligodendrocytes and ependymal cells, i.e. the restriction of the multi-potential neuron/glia precursor and the glial cell fate specification. A vertebrate homologue of Gcm 1 has been identified and is expressed in the germinal zones of the developing CNS and PNS, as well as in non-neural cells. In this application, the investigator proposes to assess the involvement of the mouse Gcm 1 gene in directing neural stem cell fate in vertebrates. To that end the investigator will create lines of mice in which Gcm 1 expression is either restricted or amplified in the nestin expressing cells (neuronal and glial precursors) of the developing embryo. Embryos and postnatal animals of these lines will be analyzed by a combination of histology, immuno-microscopy and morphometry for alterations in neural cell developmental outcome. To directly assess the developmental potential of the Gcm 1 expressing cells, the investigator will isolate them by FACS sorting and place them in culture under conditions known to favor either oligodendrocyte or astrocyte differentiation. In the in vivo counterpart of the above experiments, the investigator will transplant the sorted cells into neonatal mouse brain by stereotactic injection of cell suspensions. After terminal differentiation of the graft, sections of the CNS in recipients will be examined by double label immunocytochemistry for the developmental outcome of the engrafted cells. Through this analysis, the investigator hopes to be able to identify the progeny of the transplanted tissue and determine their cell types.
| Stecca, Barbara; Nait-Oumesmar, Brahim; Kelley, Kevin A et al. (2002) Gcm1 expression defines three stages of chorio-allantoic interaction during placental development. Mech Dev 115:27-34 |
| Nait-Oumesmar, Brahim; Stecca, Barbara; Fatterpekar, Girish et al. (2002) Ectopic expression of Gcm1 induces congenital spinal cord abnormalities. Development 129:3957-64 |
