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Dev Biol. 2006 Mar 15;291(2):218-26. Epub 2006 Jan 24.

GABAergic specification in the basal forebrain is controlled by the LIM-hd factor Lhx7.

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  • 1UPR 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.

Abstract

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.

PMID:
16438949
DOI:
10.1016/j.ydbio.2005.10.023
[PubMed - indexed for MEDLINE]
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