The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
TDP-43 Is a Developmentally Regulated Protein Essential for Early Embryonic Development
Open accessAbstract
TDP-43 is a DNA/RNA-binding protein implicated in multiple steps of transcriptional and post-transcriptional regulation of gene expression. Alteration of this multifunctional protein is associated with a number of neurodegenerative diseases including amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin positive inclusions. Whereas a pathological link to neurodegenerative disorders has been established, the cellular and physiological functions of TDP-43 remain unknown. In this study, we show that TDP-43 is a nuclear protein with persistent high-level expression during embryonic development and with progressively decreased protein levels during postnatal development. In mice where the TDP-43 gene (Tardbp) was disrupted using a gene trap that carries a beta-galactosidase marker gene, heterozygous (Tardbp(+/-)) mice are fertile and healthy, but intercrosses of Tardbp(+/-) mice yielded no viable homozygotic null (Tardbp(-/-)) mice. Indeed, Tardbp(-/-) embryos die between 3.5 and 8.5 days of development. Tardbp(-/-) blastocysts grown in cell culture display abnormal expansion of their inner cell mass. The pattern of beta-galactosidase staining at E9.5 Tardbp(+/-) embryos is predominantly restricted to the neuroepithelium and remains prominent in neural progenitors at E10.5-12.5. TDP-43 is detected in spinal cord progenitors and in differentiated motor neurons as well as in the dorsal root ganglia at E12.5. Beta-galactosidase staining of tissues from adult Tardbp(+/-) mice shows widespread expression of TDP-43, including prominent levels in various regions of the central nervous system afflicted in neurodegenerative disorders. These results indicate that TDP-43 is developmentally regulated and indispensible for early embryonic development.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
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?
In the citing paper
“ALS-like phenotypes are seen in mice with partial depletion of TDP43 by RNA interference, or with targeted deletion of Tdp43 in motor neurons”
From The neurogenetics of alternative splicing (2016) · cites this paper as [164]
Citations
Cites
1 retracted
RETRACTED ARTICLE: APP binds DR6 to trigger axon pruning and neuron death via distinct caspases
Nikolaev, A., McLaughlin, T., O’Leary, D. D. M., & Tessier-Lavigne, M. (2009) · Nature · doi:10.1038/nature07767 · Cited by 992
RetractedUbiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis
Neumann, M., Sampathu, D. M., Kwong, L. K., Truax, A. C., Micsenyi, M. C., Chou, T. T., Bruce, J., Schuck, T., Grossman, M., Clark, C. M., et al. (2006) · Science · doi:10.1126/science.1134108 · Cited by 6,576
hnRNP PROTEINS AND THE BIOGENESIS OF mRNA
Dreyfuss, G., Matunis, M. J., Piñol-Roma, S., & Burd, C. G. (1993) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.62.070193.001445 · Cited by 1,558
TDP‐43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease
Amador‐Ortiz, C., Lin, W., Ahmed, Z., Personett, D., Davies, P., Duara, R., Graff‐Radford, N. R., Hutton, M. L., & Dickson, D. W. (2007) · Annals of Neurology · doi:10.1002/ana.21154 · Cited by 916
Ou, S.-H. I., Wu, F. K., Harrich, D., Garcı́a-Martı́nez, L. F., & Gaynor, R. B. (1995) · Journal of Virology · doi:10.1128/jvi.69.6.3584-3596.1995 · Cited by 762
TDP-43 mutant transgenic mice develop features of ALS and frontotemporal lobar degeneration
Wegorzewska, I., Bell, S., Cairns, N. J., Miller, T. M., & Baloh, R. H. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908767106 · Cited by 706
Nuclear factor TDP‐43 and SR proteins promote in vitro and in vivo CFTR exon 9 skipping
Buratti, E., Dörk, T., Zuccato, E., Pagani, F., Romano, M., & Baralle, F. E. (2001) · The EMBO Journal · doi:10.1093/emboj/20.7.1774 · Cited by 633
Aberrant cleavage of TDP-43 enhances aggregation and cellular toxicity
Zhang, Y., Xu, Y.-F., Cook, C. N., Gendron, T. F., Roettges, P. S., Link, C. D., Lin, W.-L., Tong, J., Castanedes‐Casey, M., Ash, P. E. A., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900688106 · Cited by 614
Rethinking ALS: The FUS about TDP-43
Lagier‐Tourenne, C., & Cleveland, D. W. (2009) · Cell · doi:10.1016/j.cell.2009.03.006 · Cited by 596
Multiple roles of TDP-43 in gene expression, splicing regulation, and human disease
Buratti, E. (2007) · Frontiers in bioscience · doi:10.2741/2727 · Cited by 493
TDP-43 Binds Heterogeneous Nuclear Ribonucleoprotein A/B through Its C-terminal Tail
Buratti, E., Brindisi, A., Giombi, M., Tisminetzky, S. G., Ayala, Y. M., & Baralle, F. E. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505557200 · Cited by 474
Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases
Nakashima-Yasuda, H., Uryu, K., Robinson, J., Xie, S. X., Hurtig, H., Duda, J. E., Arnold, S. E., Siderowf, A., Grossman, M., Leverenz, J. B., et al. (2007) · Acta Neuropathologica · doi:10.1007/s00401-007-0261-2 · Cited by 468
Glial specification in the vertebrate neural tube
Rowitch, D. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1389 · Cited by 432
Ayala, Y. M., Pantano, S., D’Ambrogio, A., Buratti, E., Brindisi, A., Marchetti, C., Romano, M., & Baralle, F. E. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.02.038 · Cited by 382
Igaz, L. M., Kwong, L. K., Chen‐Plotkin, A. S., Winton, M. J., Unger, T. L., Xu, Y., Neumann, M., Trojanowski, J. Q., & Lee, V. M. ‐. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m809462200 · Cited by 367
TDP43 is a human low molecular weight neurofilament (hNFL) mRNA-binding protein
Strong, M. J., Volkening, K., Hammond, R. R., Yang, W., Strong, W., Leystra‐Lantz, C., & Shoesmith, C. L. (2007) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2007.03.007 · Cited by 362
Specification of dorsal spinal cord interneurons
Helms, A. W., & Johnson, J. E. B. (2003) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(03)00010-2 · Cited by 357
Depletion of TDP‐43 affects Drosophila motoneurons terminal synapsis and locomotive behavior
Feiguin, F. M., Godena, V. K., Romano, G., D’Ambrogio, A., Klima, R., & Baralle, F. E. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.04.019 · Cited by 310
Structural diversity and functional implications of the eukaryotic TDP gene family
Wang, H., Wang, I., Bose, J. K., & Shen, C. ‐. J. (2003) · Genomics · doi:10.1016/s0888-7543(03)00214-3 · Cited by 306
Cocaine Regulates MEF2 to Control Synaptic and Behavioral Plasticity
Pulipparacharuvil, S., Renthal, W., Hale, C. F., Taniguchi, M., Xiao, G., Kumar, A., Russo, S. J., Sikder, D., Dewey, C. M., Davis, M. M., et al. (2008) · Neuron · doi:10.1016/j.neuron.2008.06.020 · Cited by 281
Self-citationTDP‐43, a neuro‐pathosignature factor, is essential for early mouse embryogenesis
Wu, L., Cheng, W., Hou, S., Yan, Y., Jiang, S., & Shen, C. ‐. J. (2010) · genesis · doi:10.1002/dvg.20584 · Cited by 256
ARE‐mRNA degradation requires the 5′–3′ decay pathway
Stoecklin, G., Mayo, T., & Anderson, P. (2005) · EMBO Reports · doi:10.1038/sj.embor.7400572 · Cited by 237
Ayala, Y. M., Misteli, T., & Baralle, F. E. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800546105 · Cited by 235
Mercado, P. A. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki897 · Cited by 226
Bose, J. K., Wang, I., Li, H., Tarn, W., & Shen, C. ‐. J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m805376200 · Cited by 172
TDP-43: a novel neurodegenerative proteinopathy
Forman, M. S., Trojanowski, J. Q., & Lee, V. M. ‐. (2007) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2007.08.005 · Cited by 126
Chapter 1 The Molecular Links Between TDP‐43 Dysfunction and Neurodegeneration
Buratti, E., & Baralle, F. E. (2009) · Advances in genetics · doi:10.1016/s0065-2660(09)66001-6 · Cited by 102
TDP-43 Depletion Induces Neuronal Cell Damage through Dysregulation of Rho Family GTPases
Iguchi, Y., Katsuno, M., Niwa, J.-I., Yamada, S.-I., Sone, J., Waza, M., Adachi, H., Tanaka, F., Nagata, K., Arimura, N., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.012195 · Cited by 102
TDP-43 localizes in mRNA transcription and processing sites in mammalian neurons
Casafont, Í., Bengoechea, R., Tapia, O., Berciano, M. T., & Lafarga, M. (2009) · Journal of Structural Biology · doi:10.1016/j.jsb.2009.06.006 · Cited by 81
Specificity of Ca2+-Dependent Protein Interactions Mediated by the C2A Domains of Synaptotagmins
Sugita, S., & Südhof, T. C. (2000) · Biochemistry · doi:10.1021/bi9920984 · Cited by 59
Synaptic expression of the high-affinity kainate receptor subunit KA2 in hippocampal cultures
Roche, K. W., & Huganir, R. L. (1995) · Neuroscience · doi:10.1016/0306-4522(95)00253-f · Cited by 53
Flagged first, then by citations
Cited by
Sorted by citations
Converging Mechanisms in ALS and FTD: Disrupted RNA and Protein Homeostasis
Ling, S.-C., Polymenidou, M., & Cleveland, D. W. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.033 · Cited by 1,811
TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration
Lagier-Tourenne, C., Polymenidou, M., & Cleveland, D. W. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq137 · Cited by 1,021
TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia
Mackenzie, I. R., Rademakers, R., & Neumann, M. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70195-2 · Cited by 1,012
Molecular Mechanisms of TDP-43 Misfolding and Pathology in Amyotrophic Lateral Sclerosis
Prasad, A., Bharathi, V., Sivalingam, V., Girdhar, A., & Patel, B. K. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00025 · Cited by 817
ALS Genetics, Mechanisms, and Therapeutics: Where Are We Now?
Mejzini, R., Flynn, L. L., Pitout, I. L., Fletcher, S., Wilton, S. D., & Akkari, P. A. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.01310 · Cited by 803
Metadata
- Authors
- Sephton, C. F., Good, S. K., Atkin, S., Dewey, C. M., Mayer, P., Herz, J., & Yu, G.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Yu, Gang
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 285
- Issue
- 9
- Pages
- 6826-6834
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2825476
- OpenAlex
- W2069350252
- Cited by
- 370
- References
- 31
- Citations by year
- 2026: 8 · 2025: 17 · 2024: 12 · 2023: 22 · 2022: 30 · 2021: 24 · 2020: 17 · 2019: 23 · 2018: 25 · 2017: 20 · 2016: 17 · 2015: 17 · 2014: 32 · 2013: 30 · 2012: 25
- FWCI
- 15.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG023104, R01AG029547, R01AG023104)
- National Heart, Lung, and Blood Institute (R37HL063762)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- TDP-43, TARDBP, embryonic development, gene trap, conditional knockout mice, neural progenitor cells, neuroepithelium, motor neurons, dorsal root ganglia, developmental regulation, neurodegenerative diseases, amyotrophic lateral sclerosis, frontotemporal lobar degeneration, ubiquitin-positive inclusions
- MeSH terms
- Animals, Animals, Newborn, Blastocyst, Central Nervous System, DNA-Binding Proteins, Heterozygote, Homozygote, Neurons, Stem Cells, Tissue Distribution, Gene Expression Regulation, Developmental, Neurodegenerative Diseases, Embryonic Development, Mice
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
