Active suppression of interneuron programs within developing motor neurons revealed by analysis of homeodomain factor HB9
Open accessAbstract
Sonic hedgehog (Shh) specifies the identity of both motor neurons (MNs) and interneurons with morphogen-like activity. Here, we present evidence that the homeodomain factor HB9 is critical for distinguishing MN and interneuron identity in the mouse. Presumptive MN progenitors and postmitotic MNs express HB9, whereas interneurons never express this factor. This pattern resembles a composite of the avian homologs MNR2 and HB9. In mice lacking Hb9, the genetic profile of MNs is significantly altered, particularly by upregulation of Chx10, a gene normally restricted to a class of ventral interneurons. This aberrant gene expression is accompanied by topological disorganization of motor columns, loss of the phrenic and abducens nerves, and intercostal nerve pathfinding defects. Thus, MNs actively suppress interneuron genetic programs to establish their identity.
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The balance between V2a interneurons and motor neurons is linked, and loss of motor neurons in Olig1/2 knockout mice increases Chx10+ V2a interneurons.
“The balance between V2a interneurons and motor neurons is known to be linked (Thaler et al., 1999), and loss of motor neurons in Olig1/2 knockout mice results in a dramatic increase of Chx10+ V2a interneurons”
From Generation of Functional Human 3D Cortico-Motor Assembloids (2020) · cites this paper as Thaler et al., 1999
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- Authors
- Thaler, J., Harrison, K., Sharma, K., Lettieri, K., Kehrl, J., & Pfaff, S. L.
- Affiliations
- Salk Institute for Biological Studies (US)
- National Institutes of Health (US)
- Corresponding author
- Pfaff, Samuel L
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1999-08
- Volume
- 23
- Issue
- 4
- Pages
- 675-687
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W1993982470
- Cited by
- 354
- References
- 52
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 6 · 2023: 13 · 2022: 16 · 2021: 6 · 2020: 9 · 2019: 13 · 2018: 9 · 2017: 3 · 2016: 10 · 2015: 16 · 2014: 13 · 2013: 13 · 2012: 26
- FWCI
- 5.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS37116)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Keywords
- HB9, motor neurons, interneurons, Sonic hedgehog, neuronal identity specification, Chx10, phrenic nerve, abducens nerve, neural progenitor differentiation
- MeSH terms
- Animals, Axons, Cell Differentiation, Chick Embryo, Genes, Homeobox, Immunohistochemistry, Interneurons, Mice, Transgenic, Mitosis, Motor Neurons, Repressor Proteins, Stem Cells, Transcription Factors, Xenopus laevis, In Situ Hybridization, Homeodomain Proteins, Gene Expression Regulation, Developmental, Xenopus Proteins, Mice, Hedgehog Proteins
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