title: The LIM-homeobox gene Lhx8 is required for the development of many cholinergic neurons in the mouse forebrain.
abstract: Forebrain cholinergic neurons play important roles as striatal local circuit neurons and basal telencephalic projection neurons. The genetic mechanisms that control development of these neurons suggest that most of them are derived from the basal telencephalon where Lhx8, a LIM-homeobox gene, is expressed. Here we report that mice with a null mutation of Lhx8 are deficient in the development of forebrain cholinergic neurons. Lhx8 mutants lack the nucleus basalis, a major source of the cholinergic input to the cerebral cortex. In addition, the number of cholinergic neurons is reduced in several other areas of the subcortical forebrain in Lhx8 mutants, including the caudate-putamen, medial septal nucleus, nucleus of the diagonal band, and magnocellular preoptic nucleus. Although cholinergic neurons are not formed, initial steps in their specification appear to be preserved, as indicated by a presence of cells expressing a truncated Lhx8 mRNA and mRNA of the homeobox gene Gbx1. These results provide genetic evidence supporting an important role for Lhx8 in development of cholinergic neurons in the forebrain.
authors.affiliation: Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, Bethesda, MD 20892,USA.
authors.forename: Yangu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Oscar
authors.initials: O
authors.lastname: Marín
authors.forename: Edit
authors.initials: E
authors.lastname: Hermesz
authors.forename: Aaron
authors.initials: A
authors.lastname: Powell
authors.forename: Nuria
authors.initials: N
authors.lastname: Flames
authors.forename: Miklós
authors.initials: M
authors.lastname: Palkovits
authors.forename: John L R
authors.initials: JL
authors.lastname: Rubenstein
authors.forename: Heiner
authors.initials: H
authors.lastname: Westphal
mesh_terms: D000818:Animals; D002799:Cholinergic Fibers / Q000378:metabolism / Q000648:ultrastructure; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007395:Interneurons / Q000166:cytology / Q000378:metabolism; D060850:LIM-Homeodomain Proteins; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D016548:Prosencephalon / Q000196:embryology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013687:Telencephalon / Q000196:embryology / Q000378:metabolism; D014157:Transcription Factors
chemical_list: D018398:Homeodomain Proteins; C112960:LIM homeobox protein 8; D060850:LIM-Homeodomain Proteins; D012333:RNA, Messenger; D014157:Transcription Factors