PTBP1 Is Required for Embryonic Development before Gastrulation
Open accessAbstract
Polypyrimidine-tract binding protein 1 (PTBP1) is an important cellular regulator of messenger RNAs influencing the alternative splicing profile of a cell as well as its mRNA stability, location and translation. In addition, it is diverted by some viruses to facilitate their replication. Here, we used a novel PTBP1 knockout mouse to analyse the tissue expression pattern of PTBP1 as well as the effect of its complete removal during development. We found evidence of strong PTBP1 expression in embryonic stem cells and throughout embryonic development, especially in the developing brain and spinal cord, the olfactory and auditory systems, the heart, the liver, the kidney, the brown fat and cartilage primordia. This widespread distribution points towards a role of PTBP1 during embryonic development. Homozygous offspring, identified by PCR and immunofluorescence, were able to implant but were arrested or retarded in growth. At day 7.5 of embryonic development (E7.5) the null mutants were about 5x smaller than the control littermates and the gap in body size widened with time. At mid-gestation, all homozygous embryos were resorbed/degraded. No homozygous mice were genotyped at E12 and the age of weaning. Embryos lacking PTBP1 did not display differentiation into the 3 germ layers and cavitation of the epiblast, which are hallmarks of gastrulation. In addition, homozygous mutants displayed malformed ectoplacental cones and yolk sacs, both early supportive structure of the embryo proper. We conclude that PTBP1 is not required for the earliest isovolumetric divisions and differentiation steps of the zygote up to the formation of the blastocyst. However, further post-implantation development requires PTBP1 and stalls in homozygous null animals with a phenotype of dramatically reduced size and aberration in embryonic and extra-embryonic structures.
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Germline knockout of Ptbp1 in mice leads to early embryonic mortality.
“Germline knockout of Ptbp1 in mice leads to early embryonic mortality22,23.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [22]
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“PTBP1 suppression of entry into S-phase was unanticipated since in other systems, including germinal centre (GC) B cells, PTBP1 promoted proliferation (Suckale et al., 2011; Shibayama et al., 2009; La Porta et al., 2016) and progression through late S-phase (Monzon-Casanova et al., 2018).”
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“It is expressed in the heart, skeletal muscle and the brain and is important for early embryonic development as the knockout is lethal (17).”
BackgroundA new function of ROD1 in nonsense‐mediated mRNA decay
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“The most thoroughly-characterized regulator of preproinsulin mRNA stability, and thereby discussed here in greater length, is the ubiquitous RNA-binding protein PTBP1 (also known as PTB or hnRNP I – heterogeneous nuclear ribonucleoprotein I), which is essential for mammalian development already at early stages of gast…”
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Self-citationPtbp1 and Exosc9 knockdowns trigger skin stability defects through different pathways
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PTBP1 contributes to spermatogenesis through regulation of proliferation in spermatogonia
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“Suckale et al. [48] demonstrated was highly expressed in embryonic stem throughout embryonic development, which PTBP1 plays an essential role in early embryonic .”
RetractedChen, L., Pan, X., Zeng, T., Zhang, Y., Huang, T., & Cai, Y. (2019) · IEEE Access · doi:10.1109/access.2019.2939556 · Cited by 13 · see citing works
“As an important cellular regulator of mRNAs, PTBP1 can influence the alternative splicing profile of a cell to change the stability, location, and translation of its regulated mRNA, which can regulate the embryonic and extra-embryonic structures required for embryonic development before gastrulation [7].”
BackgroundPolypyrimidine tract binding protein 1 regulates the activation of mouse CD8 T cells
D’Angeli, V., Monzón‐Casanova, E., Matheson, L. S., Gizlenci, Ö., Petkau, G., Gooding, C., Berrens, R. V., Smith, C. W. J., & Turner, M. (2022) · European Journal of Immunology · doi:10.1002/eji.202149781 · Cited by 13 · see citing works
Zhang, Y., Lai, J., Wang, X., Li, M., Zhang, Y., Ji, C., Chen, Q., & Lu, S. (2023) · Archives animal breeding/Archiv für Tierzucht · doi:10.5194/aab-66-357-2023 · Cited by 12 · see citing works
Post-transcriptional regulation of the transcriptional apparatus in neuronal development
Nazim, M. (2024) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2024.1483901 · Cited by 11 · see citing works
“Knockout of Ptbp1 in mouse germline results in early embryonic lethality, implicating that many PTBP1 splicing targets are involved in maintaining pluripotency and inhibiting differentiation (Shibayama et al., 2009; Suckale et al., 2011).”
Uncovering RNA binding proteins associated with age and gender during liver maturation
Chaturvedi, P., Neelamraju, Y., Arif, W., Kalsotra, A., & Janga, S. C. (2015) · Scientific Reports · doi:10.1038/srep09512 · Cited by 12 · see citing works
Noiret, M., Audic, Y., & Hardy, S. (2012) · The International Journal of Developmental Biology · doi:10.1387/ijdb.120017sh · Cited by 11 · see citing works
“…zone; FXR1, fragile X mental retardation syndrome-related protein 1; NMD, nonsense-mediated decay; PTB, polypryrimidine tract binding protein; RBP, RNA binding protein; UFE, unfertilized egg. knockout results in lethality shortly after implantation (Shibayama et al., 2009; Suckale et al., 2011).”
BackgroundFontana, L., Rovina, D., Novielli, C., Maffioli, E., Tedeschi, G., Magnani, I., & Larizza, L. (2015) · Cancer Letters · doi:10.1016/j.canlet.2014.12.049 · Cited by 11 · see citing works
Wdhd1 is essential for early mouse embryogenesis
Fan, H.-H., Lee, K.-H., Chen, Y., Lin, L.-J., Yang, T., Lin, S., & Yu, I. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2021.119011 · Cited by 9 · see citing works
RNA processing in neurological tissue: development, aging and disease
Szeto, R. A., Tran, T. H., Truong, J., Negraes, P. D., & Trujillo, C. A. (2020) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2020.09.004 · Cited by 8 · see citing works
Monzón‐Casanova, E., Bates, K. J., Smith, C. W. J., & Turner, M. (2021) · European Journal of Immunology · doi:10.1002/eji.202149257 · Cited by 8 · see citing works
Salmén, F., Jonghe, J. D., Kamiński, T. S., Alemany, A., Parada, G. E., Verity-Legg, J., Yanagida, A., Kohler, T. N., Battich, N., van den Brekel, F., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.09.15.460240 · Cited by 8 · see citing works
“…with cell types involved in heart morphogenesis, early gastrulation, extra-embryonic tissues and blood development, showing widespread involvement of AS in these processes (Baralle and Giudice, 2017; Conboy, 2017; Kalsotra et al., 2008; Li et al., 2020; Pimentel et al., 2013; Suckale et al., 2011).”
BackgroundSENOO, M., HOZOJI, H., Ishikawa-Yamauchi, Y., Takijiri, T., Ohta, S., Ukai, T., Kabata, M., Yamamoto, T., Yamada, Y., Ikawa, M., et al. (2020) · Journal of Reproduction and Development · doi:10.1262/jrd.2020-060 · Cited by 7 · see citing works
“Conversely, conventional Ptbp1 knockout (KO) is em - bryonically lethal around gastrulation [29], and conventional Nanos3 KO results in complete infertility because of a defect in primordial germ cell development [17].”
Peter, B. (2022) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.62998 · Cited by 7 · see citing works
Noiret, M., Méreau, A., Angrand, G., Bervas, M., Gautier‐Courteille, C., Legagneux, V., Deschamps, S., Lerivray, H., Viet, J., Hardy, S., et al. (2016) · Developmental Biology · doi:10.1016/j.ydbio.2016.08.021 · Cited by 5 · see citing works
“For example, in mice, the constitutive inactivation of Ptbp1 leads to gastrulation defects with early lethality before stage 12 (Shibayama et al., 2009; Suckale et al., 2011), making the identification of altered splicing events difficult.”
BackgroundKubiak, M., Jurek, A., Kaminska, K. H., Kowalewski, J., Huang, S., & Lewandowska, M. A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20020242 · Cited by 5 · see citing works
“PTBP1 is a member of a larger family of 4 genes in mammals: PTBP1, PTBP2, PTBP3 and smPTB, characterized by a similar protein architecture and containing four RNA-recognition motifs (RRMs) [19].”
BackgroundPTBP1 : A candidate gene for intellectual disability
Alkhateeb, A. M., Habbab, W., Aburahma, S. K., & Thompson, I. R. (2017) · Meta Gene · doi:10.1016/j.mgene.2017.05.002 · Cited by 3 · see citing works
Deciphering splicing heterogeneity at single-cell resolution by SCSES
Xiao, W., Lv, X., Guo, D. H., Han, N., Zhou, L., Wang, P., & Liu, Z. (2025) · Nature Communications · doi:10.1038/s41467-025-64517-5 · Cited by 3 · see citing works
Whole-genome selective sweep analysis of Danish Large White and Chinese indigenous pig populations
Wu, X., Xiang, D., Duan, B., Zhang, W., Li, M., Ding, Y., Zhao, Z., Zhao, G., & Yin, Z. (2025) · Animal Biotechnology · doi:10.1080/10495398.2025.2467411 · Cited by 1 · see citing works
“42 Interestingly, both APC2 and PTBP1 genes were also selected in a selection signal study of LW sows with high and low estimated breeding values of total litter size.”
PTBP1 (polypyrimidine tract binding protein 1)
Fontana, L. (2012) · Atlas of Genetics and Cytogenetics in Oncology and Haematology · doi:10.4267/2042/47422 · Cited by 1 · see citing works
“Recently a strong PTBP1 expression has been found in embryonic stem cells, particularly those in the brain cortex and subventricular zone, where PTBP1 appears essential for cell division after implantation (Shibayama et al., 2009; Suckale et al., 2011).”
BackgroundPolypyrimidine Tract Binding Protein: A Universal Player in Cancer Development
Gonzalez, E., Flatt, T. G., Farooqi, M. S., Johnson, L. M., & Ahmed, A. A. (2023) · Current Molecular Medicine · doi:10.2174/0115665240251370231017053236 · Cited by 1 · see citing works
Fontana, L. (2014) · Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) · doi:10.13130/fontana-laura_phd2014-01-24
Role of post-transcriptional regulation in human liver
Chaturvedi, P. (2015) · IUScholarWorks (Indiana University) · doi:10.7912/c2/125
The regulation of incorrect splicing of ISCU in hereditary myopathy with lactic acidosis
Rawcliffe, D. F. R. (2018) · DiVA at Umeå University (Umeå University)
The effects of metabolic conditions relevant to Type 2 Diabetes on alternative splicing
Bulu, M. J. (2018) · Research Repository (Kingston University London)
Functional impact of alternative splicing in vertebrate proteomes across tissues and cell types
Rodríguez, T., & Javier, J. (2018) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas)
Tung, W., Chembazhi, U. V., Yang, J., Nguyen, K. L., Lalwani, A., Bangru, S., Yee, D., Chin, K., Kalsotra, A., & Mei, W. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.11.03.466345
“Increasing evidence indicates that PTBP1-mediated post transcriptional regulation is essential for a number of biological processes, ranging from embryonic development, neuronal cell differentiation, immune development, intestinal homeostasis, to spermatogenesis [26-34].”
BackgroundIversen, P. L. (2018) · Springer eBooks · doi:10.1007/978-3-319-98164-2_12
Qu, H., Li, X., Li, Q., Yang, X., Feng, Y., Yu, L., Qu, L., Mu, L., Zou, Y., & Chu, Y. (2023) · medRxiv · doi:10.1101/2023.07.05.23292275
“PTBP1 is closely related to the initial formation of the embryo, and PTBP1 492 serves as a factor essential for early embryonic development, especially because it is 493 necessary for rapid cell division and is essential for embryonic stem cell proliferation 494 (59).”
BackgroundMittal, K., Ataei, L., & Ramalho‐Santos, M. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.07.11.664446
Nitric oxide drives proteomic diversity through alternative splicing
Schindler, J. C., Seth, P., Hausladen, A., Chan, E. R., Yang, J., Qin, J., Qian, Z., Seth, D., Lundberg, K. C., Luna, J. M., et al. (2026) · Molecular Cell · doi:10.1016/j.molcel.2026.04.024 · Cited by 1 · see citing works
Nonsense-mediated mRNA decay and associated splicing patterns in neurodevelopmental disorders
Anisimova, P. E., Filat’eva, A. E., Tarabykin, V. S., & Kondakova, E. (2026) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2026.1914793
“Ptbp1 deficiency causes a sharp decrease in proliferative activity due to cell cycle arrest in the G2/M phase, as well as massive apoptosis (Suckale et al., 2011).”
- Authors
- Suckale, J., Wendling, O., Masjkur, J., Jäger, M., Münster, C., Anastassiadis, K., Stewart, A. F., & Solimena, M.
- Affiliations
- Paul Langerhans Institute Dresden (DE)
- Institut de génétique et de biologie moléculaire et cellulaire (FR)
- Center for Regenerative Therapies Dresden (DE)
- Technische Universität Dresden (DE)
- Max Planck Institute of Molecular Cell Biology and Genetics (DE)
- Corresponding author
- Solimena, Michele
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-02-17
- Volume
- 6
- Issue
- 2
- Pages
- e16992
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3040740
- OpenAlex
- W2075886645
- Cited by
- 55
- References
- 46
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 4 · 2022: 5 · 2021: 4 · 2020: 4 · 2019: 3 · 2018: 10 · 2017: 3 · 2016: 3 · 2015: 4 · 2014: 1 · 2013: 2 · 2012: 6
- FWCI
- 1.17
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Site cant be reached (submittedVersion, cc-by)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Qucosa (Saxon State and University Library Dresden) (submittedVersion, cc-by)
- univOAK (4 institutions : Université de Strasbourg, Université de Haute Alsace, INSA Strasbourg, Bibliothèque Nationale et Universitaire de Strasbourg) (submittedVersion, cc-by)
- Funders
- Bundesministerium für Bildung und Forschung
- Technische Universität Dresden
- Max-Planck-Gesellschaft
- Zentrum für Regenerative Therapien Dresden
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- PTBP1, alternative splicing, embryonic development, gastrulation, knockout mice, embryonic stem cells, ectoplacental cone, yolk sac, blastocyst, postimplantation development, developmental arrest
- MeSH terms
- Animals, Blastocyst, Cell Differentiation, Cell Division, Embryo, Mammalian, Female, Male, Mice, Inbred C57BL, Models, Biological, Pregnancy, Time Factors, Mice, Knockout, Gene Expression Regulation, Developmental, Polypyrimidine Tract-Binding Protein, Embryonic Development, Mice, Gastrulation
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