[P1.80]: The role of three Notch ligands, delta 1, delta 4 and jagged 1 during spinal cord neurogenesis

We have previously determined the transcriptome of distinct subsets of radial glial cells at mid neurogenesis of the murine brain (Pinto et al., 2008). From this screen we selected an unknown Riken clone that we named Magellan for further analysis. Here we present the expression pattern and functional analysis of Magellan. Magellan is expressed in a subset of radial glial cells during development. Magellan localizes to the nucleus and persists into young postmitotic neurons, but is absent from more mature neurons, e.g. in the adult brain. Remarkably, Magellan is also expressed in the adult neurogenic subependymal zone, while it is absent in the subgranular zone of the dentate gyrus, the second major neurogenic niche of the adult brain. The highly basic characteristic of the protein suggests an intrinsic DNA binding capacity similar to histones or HMG proteins. Functional analysis in vitro using retroviruses to overexpress Magellan in primary cell cultures derived from the cerebral cortex of embryonic day 14 mouse embryos showed increased proliferation and self-renewal. This observation is supported in vivo utilizing in utero electroporation with overexpression of Magellan significantly increasing cell proliferation in the developing cerebral cortex. Loss-of-function and time-lapse experiments are currently performed and will be presented at the conference. In summary, Magellan is a novel nuclear protein important for neural stem cell self-renewal in embryonic and adult neurogenesis.