期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 109, 期 8, 页码 3119-3124出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1109251109
关键词
neuronal subtype specification; medial ganglionic eminence-derived interneurons
资金
- Medical Research Council
- MRC [MC_U117537087] Funding Source: UKRI
- Medical Research Council [MC_U117537087] Funding Source: researchfish
The generation and maintenance of a plethora of neuronal subtypes is essential for normal brain function. Nevertheless, little is known about the molecular mechanisms that maintain the defining characteristics of neurons following their initial postmitotic specification. Using conditional gene ablation in mice, we demonstrate here that the homeodomain protein LIM homeobox (Lhx)7 is essential for maintaining the morphological and molecular characteristics of cholinergic interneurons of the striatum. Lhx7-depleted cholinergic interneurons extinguish expression of several subtype-specific markers, including choline acetyl transferase and Isl1, and are respecified into Lhx6-expressing mature GABAergic interneurons. Additional expression studies support a model where Lhx7 controls the choice between cholinergic or GABAergic identity by gating a cross inhibitory regulation between Isl1 and Lhx6. By demonstrating that the switch between alternative striatal interneuron fates depends on persistent activity of a single transcription factor, we provide evidence that the intrinsic plasticity of mammalian forebrain neuronal subtypes is maintained after the initial specification and lineage commitment and possibly throughout life.
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