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Cited by 227Neurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene RegulationNuclear Receptors and Signaling

The LIM-homeobox gene Lhx8 is required for the development of many cholinergic neurons in the mouse forebrain

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Zhao, Yangu, Marín, Oscar, Hermesz, Edit, Powell, Aaron, Flames, Nuria, Palkovits, Miklós, Rubenstein, John L. R., Westphal, Heiner·2003·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1537759100PMC PMC166428
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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.

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  • Lhx8-Cre fate mapping suggested that these neurons account for the majority, if not all, of cholinergic projection and interneuron populations in the nucleus basalis, medial septum, and striatum, and the majority of Pvalb-positive projection neurons in the globus pallidus.

    “Genetic ‘fate-mapping’ using Lhx8-Cre suggested that these neurons account for the majority, if not all of the cholinergic projection and interneuron populations within the nucleus basalis, medial septum, and striatum, respectively, as well as the majority of Pvalb-positive projection neurons in the globus pallidus5,6”

    From Developmental diversification of cortical inhibitory interneurons (2018) · cites this paper as [6]

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Authors
Zhao, Y., Marín, O., Hermesz, E., Powell, A., Flames, N., Palkovits, M., Rubenstein, J. L. R., & Westphal, H.
Affiliations
  • Semmelweis University (HU)
  • Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, Bethesda, MD 20892; Department of Psychiatry, Nina Ireland Laboratory of Developmental Neurobiology, Langley Porter Psychiatric Institute, University of California, San Francisco, CA 94143; Department of Biochemistry, University of Szeged, P.O. Box 533, H-6701 Szeged, Hungary; and Laboratory of Neuromorphology, Semmelweis University, Tüzoltó utca 58, H-1094 Budapest, Hungary
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2003-07-10
Volume
100
Issue
15
Pages
9005-9010
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1537759100
PMC
PMC166428
OpenAlex
W2065112950
Cited by
227
References
44
Citations by year
2026: 3 · 2025: 7 · 2024: 5 · 2023: 6 · 2022: 13 · 2021: 11 · 2020: 13 · 2019: 6 · 2018: 11 · 2017: 6 · 2016: 11 · 2015: 12 · 2014: 11 · 2013: 19 · 2012: 5
FWCI
2.03
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
Funders
  • National Institutes of Health (2k02mh001046-06)
  • National Institute of Mental Health (K02 MH01046-01)
  • National Institute on Drug Abuse (R01DA012462, R01 DA12462)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
Lhx8, LIM homeobox genes, basal telencephalon, nucleus basalis of Meynert, caudate-putamen, medial septum, diagonal band of Brodmann, magnocellular preoptic nucleus, neuronal specification
MeSH terms
Animals, Cholinergic Fibers, Immunohistochemistry, Interneurons, Models, Neurological, RNA, Messenger, Telencephalon, Transcription Factors, Prosencephalon, In Situ Hybridization, Mice, Knockout, Homeodomain Proteins, Mice, LIM-Homeodomain Proteins

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