GABAergic specification in the basal forebrain is controlled by the LIM-hd factor Lhx7.
We present evidence for a temporal control of GABAergic neurotransmitter specification in the basal forebrain orchestrated by the LIM-homeodomain factor Lhx7. In Xenopus, using in vivo overexpression experiments, we show that x-Lhx7 and x-Nkx2.1 inhibit GABAergic specification in the Dlx-expressing areas of the forebrain (subpallium and diencephalon). In addition, x-Lhx7 almost totally represses GABAergic differentiation at early but not late embryonic stages in subpallial mouse primary neurons in culture, indicating that x-Lhx7 is not able to withdraw the GABAergic phenotype once it is acquired. Moreover, anatomical data show striking correlations between x-Lhx7 expression and the GABAergic/cholinergic phenotypes. These functional and anatomical observations suggest a sequential role for x-Lhx7 in neurotransmitter specification. Thus, x-Lhx7 would first prevent a pool of cells to become GABAergic early in development and then promote cholinergic differentiation later on in this pool. We propose two distinct modulatory roles for a single LIM-hd factor, depending on the developmental time window.
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UPR 2197 Développement, Evolution, Plasticité du Système Nerveux, Institut de Neurobiologie Alfred FESSARD, C.N.R.S., Avenue de la Terrasse, 91198 GIF-sur-YVETTE Cedex, France.
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D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D060850:LIM-Homeodomain Proteins; D051379:Mice; D009687:Nuclear Proteins / Q000502:physiology; D010275:Parasympathetic Nervous System / Q000166:cytology; D016548:Prosencephalon / Q000196:embryology*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000502:physiology; D014981:Xenopus; D029867:Xenopus Proteins; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018398:Homeodomain Proteins; C112960:LIM homeobox protein 8; D060850:LIM-Homeodomain Proteins; C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D029867:Xenopus Proteins; C000614411:nkx2-1 protein, Xenopus; D005680:gamma-Aminobutyric Acid