Onecut transcription factors act upstream of Isl1 to regulate spinal motoneuron diversification
Open accessAbstract
During development, spinal motoneurons (MNs) diversify into a variety of subtypes that are specifically dedicated to the motor control of particular sets of skeletal muscles or visceral organs. MN diversification depends on the coordinated action of several transcriptional regulators including the LIM-HD factor Isl1, which is crucial for MN survival and fate determination. However, how these regulators cooperate to establish each MN subtype remains poorly understood. Here, using phenotypic analyses of single or compound mutant mouse embryos combined with gain-of-function experiments in chick embryonic spinal cord, we demonstrate that the transcriptional activators of the Onecut family critically regulate MN subtype diversification during spinal cord development. We provide evidence that Onecut factors directly stimulate Isl1 expression in specific MN subtypes and are therefore required to maintain Isl1 production at the time of MN diversification. In the absence of Onecut factors, we observed major alterations in MN fate decision characterized by the conversion of somatic to visceral MNs at the thoracic levels of the spinal cord and of medial to lateral MNs in the motor columns that innervate the limbs. Furthermore, we identify Sip1 (Zeb2) as a novel developmental regulator of visceral MN differentiation. Taken together, these data elucidate a comprehensive model wherein Onecut factors control multiple aspects of MN subtype diversification. They also shed light on the late roles of Isl1 in MN fate decision.
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Onecut TFs have been shown to be expressed early in V1 and MNs.
“onecut TFs have been shown to be expressed early in V1 and MNs (Roy et al., 2012; Stam et al., 2012)”
From Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord (2019) · cites this paper as Roy et al., 2012
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- Authors
- Roy, A., Francius, C., Rousso, D. L., Seuntjens, E., Debruyn, J., Luxenhofer, G., Huber, A. B., Huylebroeck, D., Novitch, B. G., & Clotman, F.
- Affiliations
- UCLouvain (BE)
- University of California, Los Angeles (US)
- KU Leuven (BE)
- Helmholtz Munich (DE)
- Corresponding author
- Clotman, Frédéric
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2012-09-01
- Volume
- 139
- Issue
- 17
- Pages
- 3109-3119
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- PMC
- PMC4074251
- OpenAlex
- W2129091895
- Cited by
- 75
- References
- 54
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 4 · 2021: 8 · 2020: 4 · 2019: 6 · 2018: 4 · 2017: 3 · 2016: 6 · 2015: 5 · 2014: 7 · 2013: 5 · 2012: 1
- FWCI
- 2.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lirias (submittedVersion, other-oa)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion)
- Site cant be reached (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Fonds De La Recherche Scientifique - FNRS
- Fédération Wallonie-Bruxelles (10/15-026)
- Fonds Wetenschappelijk Onderzoek
- KU Leuven (GOA11/012)
- Académie Universitaire ‘Louvain
- Vlaamse regering
- Fonds Spéciaux de Recherche
- National Institute of Neurological Disorders and Stroke (R01NS072804)
- 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
- Isl1, spinal motoneurons, spinal cord development, transcriptional regulation, chick embryo
- MeSH terms
- Animals, Cell Differentiation, Chick Embryo, Fluorescent Antibody Technique, Motor Neurons, Spinal Cord, Transcription Factors, In Situ Hybridization, DNA Primers, Electroporation, Gene Expression Regulation, Developmental, Chromatin Immunoprecipitation, Mice, Onecut Transcription Factors, LIM-Homeodomain Proteins
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