Wnt5aIs a Transcriptional Target ofDlxHomeogenes and Promotes Differentiation of Interneuron ProgenitorsIn VitroandIn Vivo
Copyright policy )Wnt5aIs a Transcriptional Target ofDlxHomeogenes and Promotes Differentiation of Interneuron ProgenitorsIn VitroandIn Vivo
During brain development, neurogenesis, migration, and differentiation of neural progenitor cells are regulated by an interplay between intrinsic genetic programs and extrinsic cues. TheDlxhomeogene transcription factors have been proposed to directly control the genesis and maturation of GABAergic interneurons of the olfactory bulb (OB), subpallium, and cortex. Here we provide evidence thatDlxgenes promote differentiation of olfactory interneurons via the signaling moleculeWnt5a. Dlx2 and Dlx5 interact with homeodomain binding sequences within theWnt5alocus and activate its transcription. Exogenously providedWnt5apromotes GABAergic differentiation in dissociated OB neurons and in organ-type brain cultures. Finally, we show that the Dlx-mutant environment is unfavorable for GABA differentiation,in vivoandin vitro. We conclude thatDlxgenes favor interneuron differentiation also in a non-cell-autonomous fashion, via expression ofWnt5a.
- Dulbecco Telethon Institute Italy
- Telethon Foundation Italy
- University of Turin Italy
- University of Genoa Italy
- University of Trento Italy
Homeodomain Proteins, Chromatin Immunoprecipitation, Epidermal Growth Factor, Glutamate Decarboxylase, MAP Kinase Kinase 4, Green Fluorescent Proteins, neural stem-cells; olfactory-bulb interneurons; central-nervous-system; neuronal differentiation; gabaergic interneurosns; subventricular zone; homeobox genes; axon guidance; cortical neurogenesis; signaling promotes, Brain, Gene Expression Regulation, Developmental, Cell Differentiation, Mice, Transgenic, Embryo, Mammalian, Models, Biological, Coculture Techniques, Mice, Animals, Newborn, Interneurons, Chlorocebus aethiops, Neural Stem cells; Central Nervous System; development, Animals, Fibroblast Growth Factor 2, Cells, Cultured
Homeodomain Proteins, Chromatin Immunoprecipitation, Epidermal Growth Factor, Glutamate Decarboxylase, MAP Kinase Kinase 4, Green Fluorescent Proteins, neural stem-cells; olfactory-bulb interneurons; central-nervous-system; neuronal differentiation; gabaergic interneurosns; subventricular zone; homeobox genes; axon guidance; cortical neurogenesis; signaling promotes, Brain, Gene Expression Regulation, Developmental, Cell Differentiation, Mice, Transgenic, Embryo, Mammalian, Models, Biological, Coculture Techniques, Mice, Animals, Newborn, Interneurons, Chlorocebus aethiops, Neural Stem cells; Central Nervous System; development, Animals, Fibroblast Growth Factor 2, Cells, Cultured
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