Cited by 376Developmental Biology and Gene RegulationAxon Guidance and Neuronal SignalingNeurogenesis and neuroplasticity mechanisms

Hox repertoires for motor neuron diversity and connectivity gated by a single accessory factor, FoxP1

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Dasen, Jeremy S., De Camilli, Alessandro, Wang, Bin, Tucker, Philip W., Jessell, Thomas M.·2008·Cell

Abstract

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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Crossref · 10.1016/j.cell.2008.06.019

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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”

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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
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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