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[P1.18]: Inhibition of gliogenesis and promotion of neuronogenesis by patterned overexpression of Emx2 and Foxg1
Author(s) -
Brancaccio M.,
Pivetta C.,
Granzotto M.,
Filippis C.,
Mallamaci A.
Publication year - 2010
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2010.07.059
Subject(s) - gliogenesis , citation , promotion (chess) , computer science , library science , world wide web , biology , political science , genetics , law , progenitor cell , stem cell , politics
Neural stem cells (NSCs) give rise to all cell types forming the cortex, neurons, astrocytes and oligodendrocytes. The transition from the former to the latter ones takes place via lineage-restricted progenitors and is mastered by large sets of genes, among which some implicated in CNS pattern formation. Aim of this study was to disentangle the kinetic and histogenetic roles exerted by two of these genes, Emx2 and Foxg1, in cortico-cerebral precursors. An integrated in vitro assay design was set up for this analysis. Early embryonic cortical progenitors were trasduced with lentiviral vectors driving overexpression of Emx2 and Foxg1 in NSCs or neuronal progenitors (NPs) and were kept under proproliferative or pro-differentiative culture conditions for different times. Cells belonging to different neuronogenic and gliogenic compartments were labeled by spectrally distinguishable fluoroproteins, driven by cell-type-specific promoters, as well as by cell-type-specific antibodies. They were subsequently scored, via multiplex cytofluorometry and immuno-cytofluorescence. Finally, these conditional gain-of-function assays were complemented by similar (immuno)fluorocytometric profiling of neural cultures constitutively loss-of-function for each of these two genes. A detailed picture of Emx2 and Foxg1 activities in corticocerebral histogenesis resulted from this study. We found that Foxg1 inhibits gliogenic commitment of neural stem cells. Moreover, it augments their neuronal output, by inhibiting them and neuronally committed progenitors from leaving cell cycle. Finally, the same gene, when over expressed in neuronal progenitors, further stimulates neurite outgrowth which subsequently occurs in their post-mitotic progenies. Conversely, Emx2, while early promoting neural stem cell self-renewal, later strongly pushes these cells to differentiate, along both the neuronogenic and the gliogenic lineages. Patterned overexpression of Foxg1 and/or Emx2 may be exploited to substantially ameliorate the absolute and relative neuronal outputs obtainable from neural cultures, for purposes of cell-based brain repair.