title: Cux-1 and Cux-2 control the development of Reelin expressing cortical interneurons.
abstract: Homeodomain transcription factors play important roles in the specification and differentiation of neuronal subpopulations. In the cerebral cortex, the expression patterns of Cux-1 and Cux-2 in the medial ganglionic eminence (MGE) suggest a role for these transcription factors in the development of interneurons, a heterogeneous neuronal population. In this report, we describe expression of Cux-1 and Cux-2 proteins in Reelin-secreting interneurons of the cortical plate, but not in calretinin or parvalbumin subpopulations. The role of Cux genes in the development of Reelin positive neurons was studied using Cux-1 and Cux-2 knockout mice. These experiments demonstrate that Cux-1-/-; Cux-2-/- double mutation is embryonically lethal. Although this phenotype is highly penetrant, a small proportion of mice develop to birth (P0). Analysis of these animals demonstrate that expression of Reelin is completely absent in layers II-IV of Cux-1-/-; Cux-2-/- double mutant mice, but it is not affected in the cortex of Cux-1-/- or Cux-2-/- single mutants. No Cux-1-/-; Cux-2-/- double-mutant were collected after P0. Since, GABA-ergic populations mature at late postnatal stages, this did not allow us to analyze the expression of subclass specific markers and define the affected interneuron subpopulations. Our analysis of Cux-1-/-; Cux-2-/- double mutant thus demonstrates essential yet redundant roles for Cux-1 and Cux-2 in specifying Reelin expressing cortical interneurons.
authors.affiliation: Centro Nacional de Biotecnología, CSIC, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Cubelos
authors.forename: Alvaro
authors.initials: A
authors.lastname: Sebastián-Serrano
authors.forename: Seonhee
authors.initials: S
authors.lastname: Kim
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Redondo
authors.forename: Christopher
authors.initials: C
authors.lastname: Walsh
authors.forename: Marta
authors.initials: M
authors.lastname: Nieto
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology / Q000254:growth & development; D004622:Embryo, Mammalian; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D007395:Interneurons / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000172:deficiency / Q000502:physiology*; D000091042:Reelin Protein; D012097:Repressor Proteins / Q000502:physiology*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C000624101:Cux1 protein, mouse; C101672:Cux2 protein, mouse; D016326:Extracellular Matrix Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D000091042:Reelin Protein; D012097:Repressor Proteins; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases