title: Wnt5a is a transcriptional target of Dlx homeogenes and promotes differentiation of interneuron progenitors in vitro and in vivo.
abstract: During brain development, neurogenesis, migration, and differentiation of neural progenitor cells are regulated by an interplay between intrinsic genetic programs and extrinsic cues. The Dlx homeogene 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 that Dlx genes promote differentiation of olfactory interneurons via the signaling molecule Wnt5a. Dlx2 and Dlx5 interact with homeodomain binding sequences within the Wnt5a locus and activate its transcription. Exogenously provided Wnt5a promotes 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 vivo and in vitro. We conclude that Dlx genes favor interneuron differentiation also in a non-cell-autonomous fashion, via expression of Wnt5a.
authors.affiliation: Dulbecco Telethon Institute c/o Molecular Biotechnology Center, University of Torino, 10126 Torino, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Paina
authors.forename: Donatella
authors.initials: D
authors.lastname: Garzotto
authors.forename: Silvia
authors.initials: S
authors.lastname: DeMarchis
authors.forename: Marco
authors.initials: M
authors.lastname: Marino
authors.forename: Alessia
authors.initials: A
authors.lastname: Moiana
authors.forename: Luciano
authors.initials: L
authors.lastname: Conti
authors.forename: Elena
authors.initials: E
authors.lastname: Cattaneo
authors.forename: Marzia
authors.initials: M
authors.lastname: Perera
authors.forename: Giorgio
authors.initials: G
authors.lastname: Corte
authors.forename: Enzo
authors.initials: E
authors.lastname: Calautti
authors.forename: Giorgio R
authors.initials: GR
authors.lastname: Merlo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D047369:Chromatin Immunoprecipitation / Q000379:methods; D018920:Coculture Techniques; D004622:Embryo, Mammalian; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D007395:Interneurons / Q000502:physiology*; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology; D040081:Protein Array Analysis / Q000379:methods; D013997:Time Factors; D014162:Transfection / Q000379:methods; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D000071818:Wnt-5a Protein; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C501120:Dlx5 protein, mouse; C100597:Dlx6 protein, mouse; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; D051176:beta Catenin; D016222:Fibroblast Growth Factor 2; D049452:Green Fluorescent Proteins; D005680:gamma-Aminobutyric Acid; D004815:Epidermal Growth Factor; D048670:MAP Kinase Kinase 4; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1