title: The ascl1a and dlx genes have a regulatory role in the development of GABAergic interneurons in the zebrafish diencephalon.
abstract: During development of the mouse forebrain interneurons, the Dlx genes play a key role in a gene regulatory network (GRN) that leads to the GABAergic phenotype. Here, we have examined the regulatory relationships between the ascl1a, dlx, and gad1b genes in the zebrafish forebrain. Expression of ascl1a overlaps with dlx1a in the telencephalon and diencephalon during early forebrain development. The loss of Ascl1a function results in a loss of dlx expression, and subsequent losses of dlx5a and gad1b expression in the diencephalic prethalamus and hypothalamus. Loss of Dlx1a and Dlx2a function, and, to a lesser extent, of Dlx5a and Dlx6a, impairs gad1b expression in the prethalamus and hypothalamus. We conclude that dlx1a/2a act downstream of ascl1a but upstream of dlx5a/dlx6a and gad1b to activate GABAergic specification. This pathway is conserved in the diencephalon, but has diverged between mammals and teleosts in the telencephalon.
authors.affiliation: Center for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, ON, Canada, K1N 6N5.
authors.forename: Ryan B
authors.initials: RB
authors.lastname: MacDonald
authors.forename: Jacob N
authors.initials: JN
authors.lastname: Pollack
authors.forename: Mélanie
authors.initials: M
authors.lastname: Debiais-Thibaud
authors.forename: Eglantine
authors.initials: E
authors.lastname: Heude
authors.forename: Jared Coffin
authors.initials: JC
authors.lastname: Talbot
authors.forename: Marc
authors.initials: M
authors.lastname: Ekker
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D004027:Diencephalon / Q000378:metabolism; D059330:GABAergic Neurons / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D005968:Glutamate Decarboxylase / Q000502:physiology*; D018398:Homeodomain Proteins / Q000502:physiology*; D007031:Hypothalamus / Q000378:metabolism; D007395:Interneurons / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D013687:Telencephalon / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology*; D015027:Zebrafish / Q000502:physiology*; D029961:Zebrafish Proteins / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005968:Glutamate Decarboxylase; D018398:Homeodomain Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C468127:Ascl1a protein, zebrafish; C088334:Distal-less homeobox proteins; C402565:glutamate decarboxylase 1
keywords: Diencephalon; GABAergic interneuron; Telencephalon; ascl1a; dlx; gad1b