Hox repertoires for motor neuron diversity and connectivity gated by a single accessory factor, FoxP1
Open accessAbstract
The precision with which motor neurons innervate target muscles depends on a regulatory network of Hox transcription factors that translates neuronal identity into patterns of connectivity. We show that a single transcription factor, FoxP1, coordinates motor neuron subtype identity and connectivity through its activity as a Hox accessory factor. FoxP1 is expressed in Hox-sensitive motor columns and acts as a dose-dependent determinant of columnar fate. Inactivation of Foxp1 abolishes the output of the motor neuron Hox network, reverting the spinal motor system to an ancestral state. The loss of FoxP1 also changes the pattern of motor neuron connectivity, and in the limb motor axons appear to select their trajectories and muscle targets at random. Our findings show that FoxP1 is a crucial determinant of motor neuron diversification and connectivity, and clarify how this Hox regulatory network controls the formation of a topographic neural map.
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The differential gene expression analysis recovered multiple TFs with well-established differential expression patterns, including Shox2 in V2a neurons, Foxp2 in V1 neurons, Lhx4 in MNs and V2a neurons, Neurog3 and Uncx in V3 neurons, and high levels of Nr2f2, Nfia, Foxp1 and Creb5 in MNs.
“This recovered multiple TFs, many with well-established differential gene expression patterns, for example: Shox2 in V2a neurons”
From Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord (2019) · cites this paper as Dasen et al., 2008
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- Authors
- Dasen, J. S., De Camilli, A., Wang, B., Tucker, P. W., & Jessell, T. M.
- Affiliations
- Howard Hughes Medical Institute (US)
- The University of Texas at Austin (US)
- Corresponding author
- Dasen, Jeremy S.
- Jessell, Thomas M.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2008-07
- Volume
- 134
- Issue
- 2
- Pages
- 304-316
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2072808488
- Cited by
- 376
- References
- 46
- Citations by year
- 2026: 14 · 2025: 10 · 2024: 21 · 2023: 18 · 2022: 26 · 2021: 18 · 2020: 16 · 2019: 17 · 2018: 17 · 2017: 19 · 2016: 23 · 2015: 31 · 2014: 19 · 2013: 30 · 2012: 29
- FWCI
- 9.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1842 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Wellcome Trust
- U.S. Public Health Service (5R01033245)
- National Cancer Institute (CA031534, R01CA031534)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- FOXP1, Hox transcription factors, muscle innervation, neuronal identity
- MeSH terms
- Animals, Cell Differentiation, Chick Embryo, Mice, Transgenic, Motor Neurons, Repressor Proteins, Spinal Cord, Homeodomain Proteins, Gene Expression Regulation, Developmental, Green Fluorescent Proteins, Mice, Forkhead Transcription Factors
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