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Intraventricular Transplantation of Engineered Neuronal Precursors for In Vivo Neuroarchitecture Studies
Published on: May 11, 2019
Emx2 and Foxg1 inhibit gliogenesis and promote neuronogenesis
Marco Brancaccio1, Chiara Pivetta, Marilena Granzotto
1SISSA, Neurobiology Sector, Laboratory of Cerebral Cortex Development, Trieste, Italy.
Abstract:
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 immunocytofluorescence. 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.
Insights
Two key genes, Emx2 and Foxg1, were studied in neural stem cells (NSCs). Both genes inhibit glial cell formation and promote neuron generation, with potential applications in brain repair.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Neural stem cells (NSCs) generate all cortical cell types, including neurons, astrocytes, and oligodendrocytes, through regulated progenitor transitions.
- Gene expression patterns are critical in controlling central nervous system (CNS) development and cell fate determination.
Purpose of the Study:
- To investigate the roles of Emx2 and Foxg1 in regulating the differentiation of cortico-cerebral precursors.
- To elucidate the kinetic and histogenetic functions of Emx2 and Foxg1 in neural development.
Main Methods:
- Developed a novel integrated in vitro assay using lentiviral vectors for gene overexpression in embryonic cortical progenitors.
- Utilized spectrally distinguishable fluoroproteins and cell type-specific antibodies for precise cell labeling.
- Employed multiplex cytofluorometry and immunocytochemistry for quantitative analysis of cell populations.
Main Results:
- Emx2 and Foxg1 were found to inhibit gliogenesis (astrocyte and oligodendrocyte formation) and promote neuronogenesis.
- Distinct molecular mechanisms underlie the activities of Emx2 and Foxg1.
- Foxg1 significantly enhanced neurite outgrowth in addition to its effects on cell fate.
Conclusions:
- Emx2 and Foxg1 play crucial roles in cortico-cerebral histogenesis, primarily promoting neurogenesis and inhibiting gliogenesis.
- These findings suggest potential therapeutic strategies for enhancing neuronal output in cell-based brain repair applications.
