Emx2 and Foxg1 Inhibit Gliogenesis and Promote Neuronogenesis

被引:92
作者
Brancaccio, Marco
Pivetta, Chiara
Granzotto, Marilena [2 ]
Filippis, Carol
Mallamaci, Antonello [1 ]
机构
[1] SISSA, Res Area Basovizza, Lab Cerebral Cortex Dev, Neurobiol Sector, I-34012 Trieste, Italy
[2] IRCCS Burlo, Inst Maternal & Child Hlth, Immunol Lab, Trieste, Italy
关键词
Cerebral cortex; Emx2; Foxg1; Neural stem cells; Gliogenesis; Neuronogenesis; NEURAL STEM-CELLS; INTERMEDIATE PROGENITOR CELLS; EARLY CEREBRAL-CORTEX; GABAERGIC NEURONS; MAMMALIAN TELENCEPHALON; PRECURSOR CELLS; HOMEOBOX GENES; AREA IDENTITY; MUTANT MICE; INNER-EAR;
D O I
10.1002/stem.443
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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 in a highly regulated way. This process is mastered by large sets of genes, among which some implicated in central nervous system pattern formation. The 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. For this purpose, we set up a new integrated in vitro assay design. Embryonic cortical progenitors were transduced with lentiviral vectors driving overexpression of Emx2 and Foxg1 in NSCs and neuronal progenitors. Cells belonging to different neuronogenic and gliogenic compartments were labeled by spectrally distinguishable fluoroproteins driven by cell type-specific promoters and by cell type-specific antibodies and were scored via multiplex cytofluorometry and immunocyto-fluorescence. A detailed picture of Emx2 and Foxg1 activities in cortico-cerebral histogenesis resulted from this study. Unexpectedly, we found that both genes inhibit gliogenesis and promote neuronogenesis, through distinct mechanisms, and Foxg1 also dramatically stimulates neurite outgrowth. Remarkably, such activities, alone or combined, may be exploited to ameliorate the neuronal output obtainable from neural cultures, for purposes of cell-based brain repair. STEM CELLS 2010;28:1206-1218
引用
收藏
页码:1206 / 1218
页数:13
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