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Publication : The LIM-homeobox gene Islet-1 is required for the development of restricted forebrain cholinergic neurons.

First Author  Elshatory Y Year  2008
Journal  J Neurosci Volume  28
Issue  13 Pages  3291-7
PubMed ID  18367596 Mgi Jnum  J:133494
Mgi Id  MGI:3778709 Doi  10.1523/JNEUROSCI.5730-07.2008
Citation  Elshatory Y, et al. (2008) The LIM-homeobox gene Islet-1 is required for the development of restricted forebrain cholinergic neurons. J Neurosci 28(13):3291-7
abstractText  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.
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