ArticlePLoS genetics2013
Genetic and functional modularity of Hox activities in the specification of limb-innervating motor neurons.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 83 citations in OpenAlex.
- Profiling the epigenomic landscape of late embryonic and adult mouse hind limb muscles.Scientific reports · 2026Article
- Network analysis reveals potential mechanisms that determine the cellular identity of keratinocytes and corneal epithelial cells through the Hox/Gtl2-Dio3 miRNA axis.Frontiers in cell and developmental biology · 2025Article
- HOX gene expression in the developing human spine.Nature communications · 2024Article
- Modulators of Alpha-2 Macroglobulin Upregulation by High Glucose in Glomerular Mesangial Cells.Biomolecules · 2024Article
- Genome-wide screening reveals essential roles for HOX genes and imprinted genes during caudal neurogenesis of human embryonic stem cells.Stem cell reports · 2024Article
- Molecular and Cellular Mechanisms of Motor Circuit Development.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Review
- Multimodal Hox5 activity generates motor neuron diversity.Communications biology · 2024Article
- Hox genes in development and beyond.Development (Cambridge, England) · 2023Article
- Little skate genome provides insights into genetic programs essential for limb-based locomotion.eLife · 2022Article
- Nervous system-wide analysis of Hox regulation of terminal neuronal fate specification in Caenorhabditis elegans.PLoS genetics · 2022Article
- Establishing the Molecular and Functional Diversity of Spinal Motoneurons.Advances in neurobiology · 2022Article
- Diversification and Functional Evolution of HOX Proteins.Frontiers in cell and developmental biology · 2022Review
- HoxD transcription factors define monosynaptic sensory-motor specificity in the developing spinal cord.Development (Cambridge, England) · 2021Article
- Defining the signalling determinants of a posterior ventral spinal cord identity in human neuromesodermal progenitor derivatives.Development (Cambridge, England) · 2021Article
- Hox Proteins in the Regulation of Muscle Development.Frontiers in cell and developmental biology · 2021Review
- Roles ofFrontiers in cell and developmental biology · 2021Review
- Differential abilities to engage inaccessible chromatin diversify vertebrate Hox binding patterns.Development (Cambridge, England) · 2020Article
- Intrinsic control of neuronal diversity and synaptic specificity in a proprioceptive circuit.eLife · 2020Article
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Authors and funding
7 authors at 2 institutions in 1 country.
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Abstract
A critical step in the assembly of the neural circuits that control tetrapod locomotion is the specification of the lateral motor column (LMC), a diverse motor neuron population targeting limb musculature. Hox6 paralog group genes have been implicated as key determinants of LMC fate at forelimb levels of the spinal cord, through their ability to promote expression of the LMC-restricted genes Foxp1 and Raldh2 and to suppress thoracic fates through exclusion of Hoxc9. The specific roles and mechanisms of Hox6 gene function in LMC neurons, however, are not known. We show that Hox6 genes are critical for diverse facets of LMC identity and define motifs required for their in vivo specificities. Although Hox6 genes are necessary for generating the appropriate number of LMC neurons, they are not absolutely required for the induction of forelimb LMC molecular determinants. In the absence of Hox6 activity, LMC identity appears to be preserved through a diverse array of Hox5-Hox8 paralogs, which are sufficient to reprogram thoracic motor neurons to an LMC fate. In contrast to the apparently permissive Hox inputs to early LMC gene programs, individual Hox genes, such as Hoxc6, have specific roles in promoting motor neuron pool diversity within the LMC. Dissection of motifs required for Hox in vivo specificities reveals that either cross-repressive interactions or cooperativity with Pbx cofactors are sufficient to induce LMC identity, with the N-terminus capable of promoting columnar, but not pool, identity when transferred to a heterologous homeodomain. These results indicate that Hox proteins orchestrate diverse aspects of cell fate specification through both the convergent regulation of gene programs regulated by many paralogs and also more restricted actions encoded through specificity determinants in the N-terminus.
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