A Hox regulatory network establishes motor neuron pool identity and target-muscle connectivity
Open accessAbstract
Spinal motor neurons acquire specialized "pool" identities that determine their ability to form selective connections with target muscles in the limb, but the molecular basis of this striking example of neuronal specificity has remained unclear. We show here that a Hox transcriptional regulatory network specifies motor neuron pool identity and connectivity. Two interdependent sets of Hox regulatory interactions operate within motor neurons, one assigning rostrocaudal motor pool position and a second directing motor pool diversity at a single segmental level. This Hox regulatory network directs the downstream transcriptional identity of motor neuron pools and defines the pattern of target-muscle connectivity.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Pou3f1 had previously been reported in multiple neuronal subtypes of the spinal cord, e.g. in MNs, V2a and V3 interneurons, which the analysis correctly identified.
“This TF had previously been reported in multiple neuronal subtypes of the spinal cord, e.g. in MNs, V2a and V3 interneurons (Dasen et al., 2005; Francius et al., 2013), which we correctly identified.”
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., 2005
More than 50 distinct pools of MNs have been documented at limb levels of the spinal cord.
“More than 50 distinct pools of MNs have been documented at limb levels of the spinal cord (Dasen et al., 2005; Landmesser, 2001; Philippidou and Dasen, 2013).”
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., 2005
There is a large diversity of cell types in the spinal cord.
“There is a large diversity of cell types in the spinal cord. More than 50 distinct pools of MNs have been documented at limb levels of the spinal cord (Dasen et al., 2005; Landmesser, 2001; Philippidou and Dasen, 2013).”
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., 2005
Cites
A synthetic oscillatory network of transcriptional regulators
Elowitz, M., & Leibler, S. (2000) · Nature · doi:10.1038/35002125 · Cited by 4,812 · see citing works
The Molecular Biology of Axon Guidance
Tessier‐Lavigne, M., & Goodman, C. S. (1996) · Science · doi:10.1126/science.274.5290.1123 · Cited by 3,295 · see citing works
Neuronal specification in the spinal cord: inductive signals and transcriptional codes
Jessell, T. M. (2000) · Nature Reviews Genetics · doi:10.1038/35049541 · Cited by 2,089 · see citing works
Self-citationTopographic organization of embryonic motor neurons defined by expression of LIM homeobox genes
Tsuchida, T., Ensini, M., Brenner‐Morton, S., Baldassare, M., Edlund, H., Jessell, T. M., & Pfaff, S. L. (1994) · Cell · doi:10.1016/0092-8674(94)90027-2 · Cited by 997 · see citing works
Self-citationC ELL M IGRATION IN THE F OREBRAIN
Marín, Ó., & Rubenstein, J. L. R. (2003) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.26.041002.131058 · Cited by 917 · see citing works
Arber, S., Ladle, D. R., Lin, J. H., Frank, E., & Jessell, T. M. (2000) · Cell · doi:10.1016/s0092-8674(00)80859-4 · Cited by 467 · see citing works
Self-citationThe development of motor projection patterns in the chick hind limb.
Landmesser, L. T. (1978) · The Journal of Physiology · doi:10.1113/jphysiol.1978.sp012546 · Cited by 430 · see citing works
Altered segmental identity and abnormal migration of motor neurons in mice lacking Hoxb-1
Studer, M., Lumsden, A., Ariza‐McNaughton, L., Bradley, A., & Krumlauf, R. K. (1996) · Nature · doi:10.1038/384630a0 · Cited by 400 · see citing works
Motor Neuron–Derived Retinoid Signaling Specifies the Subtype Identity of Spinal Motor Neurons
Sockanathan, S., & Jessell, T. M. (1998) · Cell · doi:10.1016/s0092-8674(00)81591-3 · Cited by 389 · see citing works
Self-citationHox proteins meet more partners
Mann, R. S., & Affolter, M. (1998) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(98)80113-5 · Cited by 383 · see citing works
Motor neuron columnar fate imposed by sequential phases of Hox-c activity
Dasen, J. S., Liu, J.-P., & Jessell, T. M. (2003) · Nature · doi:10.1038/nature02051 · Cited by 381 · see citing works
Self-citationLin, J. H., Saito, T., Anderson, D. J., Lance-Jones, C. C., Jessell, T. M., & Arber, S. (1998) · Cell · doi:10.1016/s0092-8674(00)81770-5 · Cited by 334 · see citing works
Self-citationAssigning the Positional Identity of Spinal Motor Neurons
Liu, J.-P., Laufer, E., & Jessell, T. M. (2001) · Neuron · doi:10.1016/s0896-6273(01)00544-x · Cited by 329 · see citing works
Self-citationHoxa1 and Hoxb1 synergize in patterning the hindbrain, cranial nerves and second pharyngeal arch
Gavalas, A., Studer, M., Lumsden, A., Rijli, F. M., Krumlauf, R. K., & Chambon, P. (1998) · Development · doi:10.1242/dev.125.6.1123 · Cited by 325 · see citing works
Yamagata, M., Weiner, J. A., & Sanes, J. R. (2002) · Cell · doi:10.1016/s0092-8674(02)00910-8 · Cited by 322 · see citing works
Bel-Vialar, S., Itasaki, N., & Krumlauf, R. K. (2002) · Development · doi:10.1242/dev.129.22.5103 · Cited by 307 · see citing works
Regulation of motor neuron pool sorting by differential expression of type II cadherins
Price, S. R., De Marco Garcia, N. V., Ranscht, B., & Jessell, T. M. (2002) · Cell · doi:10.1016/s0092-8674(02)00695-5 · Cited by 304 · see citing works
Self-citationKania, A., & Jessell, T. M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00292-7 · Cited by 281 · see citing works
Self-citationDevelopment of the major pathways for neurite outgrowth in the chick hindlimb
Tosney, K. W., & Landmesser, L. T. (1985) · Developmental Biology · doi:10.1016/0012-1606(85)90360-4 · Cited by 272 · see citing works
ETS Gene Pea3 Controls the Central Position and Terminal Arborization of Specific Motor Neuron Pools
Livet, J., Sigrist, M., Ströbel, S., Paola, V. D., Price, S. R., Henderson, C. E., Jessell, T. M., & Arber, S. (2002) · Neuron · doi:10.1016/s0896-6273(02)00863-2 · Cited by 258 · see citing works
Self-citationSpecification of temporal identity in the developing nervous system.
Pearson, B. J., & Doe, C. (2004) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.19.111301.115142 · Cited by 254 · see citing works
Ensini, M., Tsuchida, T. N., Belting, H., & Jessell, T. M. (1998) · Development · doi:10.1242/dev.125.6.969 · Cited by 184 · see citing works
Self-citationHomeotic Transformation of Rhombomere Identity After Localized Hoxb1 Misexpression
Bell, E. J. D. H., Wingate, R. J. T., & Lumsden, A. (1999) · Science · doi:10.1126/science.284.5423.2168 · Cited by 150 · see citing works
Retinoid-X receptor signalling in the developing spinal cord
Solomin, L., Johansson, C. B., Zetterström, R. H., Bissonnette, R. P., Heyman, R. A., Olson, L., Lendahl, U., Frisén, J., & Perlmann, T. (1998) · Nature · doi:10.1038/26515 · Cited by 137 · see citing works
The acquisition of motoneuron subtype identity and motor circuit formation
Landmesser, L. T. (2001) · International Journal of Developmental Neuroscience · doi:10.1016/s0736-5748(00)00090-3 · Cited by 136 · see citing works
Anatomy and embryology of the Wing Musculature of the domestic fowl (gallus)
Sullivan, G. (1962) · Australian Journal of Zoology · doi:10.1071/zo9620458 · Cited by 130 · see citing works
Tiret, L., Mouellic, H. L., Maury, M., & Brûlet, P. (1998) · Development · doi:10.1242/dev.125.2.279 · Cited by 130 · see citing works
Gavalas, A., Ruhrberg, C., Livet, J., Henderson, C. E., & Krumlauf, R. K. (2003) · Development · doi:10.1242/dev.00802 · Cited by 124 · see citing works
Homeobox genes and pattern formation in the vertebrate limb
Izpisúa‐Belmonte, J. C., & Duboule, D. (1992) · Developmental Biology · doi:10.1016/0012-1606(92)90153-8 · Cited by 113 · see citing works
Hox Genes and Spinal Cord Development
Carpenter, E. M. (2002) · Developmental Neuroscience · doi:10.1159/000064943 · Cited by 109 · see citing works
Gaufo, G. O., Thomas, K., & Capecchi, M. (2003) · Development · doi:10.1242/dev.00730 · Cited by 95 · see citing works
Gj, R. (1941) · PubMed · Cited by 90 · see citing works
Vermot, J., Schuhbaur, B., Mouellic, H. L., McCaffery, P., Garnier, J., Hentsch, D., Brûlet, P., Niederreither, K., Chambon, P., Dollé, P., et al. (2005) · Development · doi:10.1242/dev.01718 · Cited by 86 · see citing works
Met Signaling Is Required for Recruitment of Motor Neurons to PEA3-Positive Motor Pools
Helmbacher, F., Dessaud, É., Arber, S., deLapeyrière, O., Henderson, C. E., Klein, R., & Maina, F. (2003) · Neuron · doi:10.1016/s0896-6273(03)00493-8 · Cited by 75 · see citing works
Shah, V. S., Drill, E., & Lance-Jones, C. C. (2004) · Developmental Dynamics · doi:10.1002/dvdy.20103 · Cited by 66 · see citing works
Location of motor pools innervating chick wing
Hollyday, M., & Jacobson, R. D. (1990) · The Journal of Comparative Neurology · doi:10.1002/cne.903020313 · Cited by 61 · see citing works
Theriault, F. M., Roy, P., & Stifani, S. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400768101 · Cited by 59 · see citing works
Environmental Specification of Neuronal Connectivity
Frank, E., & Wenner, P. (1993) · Neuron · doi:10.1016/0896-6273(93)90194-v · Cited by 55 · see citing works
Hoxd10induction and regionalization in the developing lumbosacral spinal cord
Lance-Jones, C. C., Omelchenko, N., Bailis, A. J., et al. (2001) · Development · doi:10.1242/dev.128.12.2255 · Cited by 53 · see citing works
Multiple phases of expression and regulation of mouse Hoxc8 during early embryogenesis
Belting, H., Shashikant, C. S., & Ruddle, F. H. (1998) · Journal of Experimental Zoology · doi:10.1002/(sici)1097-010x(199809/10)282:1/2 · Cited by 46 · see citing works
Specific guidance of motor axons to duplicated muscles in the developing amniote limb
Stirling, R. V., & Summerbell, D. (1988) · Development · doi:10.1242/dev.103.1.97 · Cited by 13 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Narendra, V., Rocha, P. P., An, D., Raviram, R., Skok, J. A., Mazzoni, E. O., & Reinberg, D. (2015) · Science · doi:10.1126/science.1262088 · Cited by 535 · see citing works
Flames, N., Pla, R., Gelman, D. M., Rubenstein, J. L. R., Puelles, L., & Marín, O. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.2750-07.2007 · Cited by 560 · see citing works
Hox Genes: Choreographers in Neural Development, Architects of Circuit Organization
Philippidou, P., & Dasen, J. S. (2013) · Neuron · doi:10.1016/j.neuron.2013.09.020 · Cited by 423 · see citing works
Self-citationDelile, J., Rayon, T., Melchionda, M., Edwards, A., Briscoe, J., & Sagner, A. (2019) · Development · doi:10.1242/dev.173807 · Cited by 356 · see citing works
Dasen, J. S., De Camilli, A., Wang, B., Tucker, P. W., & Jessell, T. M. (2008) · Cell · doi:10.1016/j.cell.2008.06.019 · Cited by 376 · see citing works
Self-citationLiu, M.-L., Zang, T., Zou, Y., Chang, J. C., Gibson, J. R., Huber, K. M., & Zhang, C.-L. (2013) · Nature Communications · doi:10.1038/ncomms3183 · Cited by 343 · see citing works
Modeling ALS with motor neurons derived from human induced pluripotent stem cells
Sances, S., Bruijn, L. I., Chandran, S., Eggan, K., Ho, R., Klim, J. R., Livesey, M. R., Lowry, E., Macklis, J. D., Rushton, D., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4273 · Cited by 289 · see citing works
Gamma and alpha motor neurons distinguished by expression of transcription factor Err3
Friese, A., Kaltschmidt, J. A., Ladle, D. R., Sigrist, M., Jessell, T. M., & Arber, S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0906809106 · Cited by 235 · see citing works
Self-citationBlum, J. A., Klemm, S., Shadrach, J. L., Guttenplan, K. A., Nakayama, L., Kathiria, A., Hoang, P. T., Gautier, O., Kaltschmidt, J. A., Greenleaf, W. J., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-020-00795-0 · Cited by 210 · see citing works
Making sense out of spinal cord somatosensory development
Lai, H. C., Seal, R. P., & Johnson, J. E. (2016) · Development · doi:10.1242/dev.139592 · Cited by 188 · see citing works
Hester, M. E., Murtha, M. J., Song, S., Rao, M., Miranda, C. J., Meyer, K., Tian, J., Boulting, G., Schaffer, D. V., Zhu, M. X., et al. (2011) · Molecular Therapy · doi:10.1038/mt.2011.135 · Cited by 183 · see citing works
Transcriptional regulation of vertebrate axon guidance and synapse formation
Polleux, F., Ince-Dunn, G., & Ghosh, A. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2118 · Cited by 168 · see citing works
Chapter 8 Hox Genes and Segmentation of the Vertebrate Hindbrain
Tümpel, S., Wiedemann, L. M., & Krumlauf, R. (2009) · Current Topics in Developmental Biology · doi:10.1016/s0070-2153(09)88004-6 · Cited by 150 · see citing works
The cellular and molecular basis of somatosensory neuron development
Meltzer, S., Santiago, C., Sharma, N., & Ginty, D. D. (2021) · Neuron · doi:10.1016/j.neuron.2021.09.004 · Cited by 149 · see citing works
Baek, M., & Mann, R. S. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.1585-09.2009 · Cited by 121 · see citing works
Cortical interneuron specification: the juncture of genes, time and geometry
Bandler, R. C., Mayer, C., & Fishell, G. (2017) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2016.10.003 · Cited by 125 · see citing works
Origin and segmental diversity of spinal inhibitory interneurons
Sweeney, L. B., Bikoff, J. B., Gabitto, M. I., Brenner-Morton, S., Baek, M., Yang, J. H., Tabak, E. G., Dasen, J. S., Kintner, C. R., & Jessell, T. M. (2018) · Neuron · doi:10.1016/j.neuron.2017.12.029 · Cited by 116 · see citing works
Self-citationGenetic dissection of GABAergic neural circuits in mouse neocortex
Taniguchi, H. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00008 · Cited by 106 · see citing works
Distinct transcriptomes define rostral and caudal serotonin neurons
Wylie, C. J., Hendricks, T. J., Zhang, B., Wang, L., Lu, P., Leahy, P., Fox, S., Maeno, H., & Deneris, E. S. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4656-09.2010 · Cited by 104 · see citing works
Francius, C., Harris, A., Rucchin, V., Hendricks, T. J., Stam, F. J., Barber, M., Kurek, D., Grosveld, F. G., Pierani, A., Goulding, M., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0070325 · Cited by 97 · see citing works
BMP4 patterns Smad activity and generates stereotyped cell fate organization in spinal organoids
Duval, N., Vaslin, C., Barata, T. C., Frarma, Y., Contremoulins, V., Baudin, X., Nedelec, S., & Ribes, V. C. (2019) · Development · doi:10.1242/dev.175430 · Cited by 93 · see citing works
Development, Maturation, and Necessity of Transcription Factors in the Mouse Suprachiasmatic Nucleus
VanDunk, C., Hunter, L. A., & Gray, P. A. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.5385-10.2011 · Cited by 89 · see citing works
Bayesian sparse regression analysis documents the diversity of spinal inhibitory interneurons
Gabitto, M. I., Pakman, A., Bikoff, J. B., Abbott, L. F., Jessell, T. M., & Paninski, L. (2016) · Cell · doi:10.1016/j.cell.2016.01.026 · Cited by 73 · see citing works
Self-citationTümpel, S., Cambronero, F., Ferretti, E., Blasi, F., Wiedemann, L. M., & Krumlauf, R. (2007) · Developmental Biology · doi:10.1016/j.ydbio.2006.10.029 · Cited by 79 · see citing works
Assembly and function of spinal circuits for motor control
Catela, C., Shin, M. M., & Dasen, J. S. (2015) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100814-125155 · Cited by 77 · see citing works
Self-citationCatela, C., Shin, M. M., Lee, D. H., Liu, J.-P., & Dasen, J. S. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.01.067 · Cited by 73 · see citing works
Self-citationMolecular Logic of Spinocerebellar Tract Neuron Diversity and Connectivity
Baek, M., Menon, V., Jessell, T. M., Hantman, A. W., & Dasen, J. S. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.04.113 · Cited by 56 · see citing works
Self-citationParallel Pbx-dependent pathways govern the coalescence and fate of motor columns
Hanley, O., Zewdu, R., Cohen, L. J., Jung, H., Lacombe, J., Philippidou, P., Lee, D. H., Selleri, L., & Dasen, J. S. (2016) · Neuron · doi:10.1016/j.neuron.2016.07.043 · Cited by 49 · see citing works
Self-citationGDE2 Regulates Subtype-Specific Motor Neuron Generation through Inhibition of Notch Signaling
Sabharwal, P., Lee, C., Park, S., Rao, M., & Sockanathan, S. (2011) · Neuron · doi:10.1016/j.neuron.2011.07.028 · Cited by 54 · see citing works
Modeling motor neuron disease: the matter of time
Arbab, M., Baars, S., & Geijsen, N. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2014.07.008 · Cited by 33 · see citing works
- Authors
- Dasen, J. S., Tice, B. C., Brenner-Morton, S., & Jessell, T. M.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Jessell, Thomas M.
- ORCID
- Dasen, Jeremy S.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2005-11
- Volume
- 123
- Issue
- 3
- Pages
- 477-491
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2122980330
- Cited by
- 461
- References
- 41
- Citations by year
- 2026: 12 · 2025: 7 · 2024: 14 · 2023: 20 · 2022: 24 · 2021: 26 · 2020: 26 · 2019: 18 · 2018: 16 · 2017: 18 · 2016: 23 · 2015: 21 · 2014: 19 · 2013: 24 · 2012: 24
- FWCI
- 9.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- 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
- Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
- Keywords
- Hox genes, motoneuron pools, spinal cord, transcriptional regulatory networks, neuronal specification, muscle innervation
- MeSH terms
- Animals, Cell Differentiation, Chick Embryo, Motor Neurons, Spinal Cord, Transcription Factors, Homeodomain Proteins, Muscle, Skeletal, Gene Expression Regulation, Developmental, Body Patterning
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
