The LIM homeobox gene, L3/Lhx8, is necessary for proper development of basal forebrain cholinergic neurons.
Basal forebrain cholinergic neurons (BFCNs) are involved in cognitive functions such as learning and memory, and are affected in several neurodegenerative diseases (e.g. Alzheimer's disease). Despite their importance, the molecular mechanisms of their development are not fully elucidated. A recent report demonstrated that some BFCNs in adult rat are positive for L3/Lhx8, a LIM homeobox transcription factor. To examine the function of L3/Lhx8 in the development of BFCNs, we generated L3/Lhx8 gene-disrupted mice. In these mice, cells expressing cholinergic neuron markers, such as choline acetyltransferase, vesicular acetylcholine transporter and p75 low-affinity NGF receptor, were markedly reduced in the basal forebrain, whereas other cholinergic neurons including brain stem and spinal motor neurons expressed the markers. Neurotransmitter phenotypes other than cholinergic in the basal forebrain appeared intact. From these results, we suggested that L3/Lhx8 has a pivotal and specific role in the development and/or maintenance of BFCNs.
Mori
Tetsuji
T
Department of Cell Science, Institute of Biomedical Sciences, Fukushima Medical University, 1 Hikarigaoka, Fukushima City, Fukushima, 960-1295 Japan.
Yuxing
Zhang
Z
Takaki
Hiromi
H
Takeuchi
Mayumi
M
Iseki
Ken
K
Hagino
Seita
S
Kitanaka
Jun-ichi
J
Takemura
Motohiko
M
Misawa
Hidemi
H
Ikawa
Masahito
M
Okabe
Masaru
M
Wanaka
Akio
A
D000818:Animals; D002799:Cholinergic Fibers / Q000378:metabolism*; D015870:Gene Expression; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D060850:LIM-Homeodomain Proteins; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics*; D010641:Phenotype; D016548:Prosencephalon / Q000254:growth & development*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors
D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C094898:Lhx3 protein; D009419:Nerve Tissue Proteins; D014157:Transcription Factors