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The Journal of Neuroscience, March 26, 2008, 28(13):3291-3297; doi:10.1523/JNEUROSCI.5730-07.2008

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Brief Communications
The LIM-Homeobox Gene Islet-1 Is Required for the Development of Restricted Forebrain Cholinergic Neurons

Yasser Elshatory^1,2,3 and Lin Gan^2,3

¹Medical Scientist Training Program, ²Interdepartmental Graduate Program in Neuroscience, ³Department of Ophthalmology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642

Correspondence should be addressed to Lin Gan, 601 Elmwood Avenue, Box 645, Rochester, NY 14642. Email: lin_gan{at}urmc.rochester.edu

Forebrain cholinergic neurons modulate complex mammalian behaviors such as reward-related learning and cognitive functions. Although their dysfunction is implicated in various psychiatric and neurodegenerative diseases, the factors governing cholinergic neuron differentiation and diversity are mostly unknown. We tested the role of the LIM-homeobox gene Isl1 in the development of forebrain cholinergic neurons by conditionally deleting Isl1 using a Six3-cre transgene. A depletion of cholinergic interneurons in the dorsal and ventral striatum, and cholinergic projection neurons in the nucleus basalis is observed and is ascribed to an early and persistent defect in cholinergic neuron differentiation. Notably, cholinergic innervation to the neocortex is abolished, whereas that to the hippocampus is unaltered. The unique pattern of cholinergic hypoinnervation encountered is supported by the presence of cholinergic projection neurons in the medial septum, the magnocellular preoptic area, and the substantia innominata. Together, these results demonstrate the requirement for Isl1 in the development of restricted telencephalic cholinergic neurons and link the development of cholinergic neurons in anatomically disparate sites to Isl1 function.

Key words: transcription factor; cholinergic neuron; differentiation; forebrain; basal forebrain; basalis; striatum

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Received Dec. 27, 2007; revised Feb. 6, 2008; accepted Feb. 14, 2008.

Correspondence should be addressed to Lin Gan, 601 Elmwood Avenue, Box 645, Rochester, NY 14642. Email: lin_gan{at}urmc.rochester.edu

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