Targeted disruption of cubilin reveals essential developmental roles in the structure and function of endoderm and in somite formation
Open accessAbstract
Background: Cubilin is a peripheral membrane protein that interacts with the integral membrane proteins megalin and amnionless to mediate ligand endocytosis by absorptive epithelia such as the extraembryonic visceral endoderm (VE). Results: Here we report the effects of the genetic deletion of cubilin on mouse embryonic development. Cubilin gene deletion is homozygous embryonic lethal with death occurring between 7.5–13.5 days post coitum (dpc). Cubilin-deficient embryos display developmental retardation and do not advance morphologically beyond the gross appearance of wild-type 8–8.5 dpc embryos. While mesodermal structures such as the allantois and the heart are formed in cubilin mutants, other mesoderm-derived tissues are anomalous or absent. Yolk sac blood islands are formed in cubilin mutants but are unusually large, and the yolk sac blood vessels fail to undergo remodeling. Furthermore, somite formation does not occur in cubilin mutants. Morphological abnormalities of endoderm occur in cubilin mutants and include a stratified epithelium in place of the normally simple columnar VE epithelium and a stratified cuboidal epithelium in place of the normally simple squamous epithelium of the definitive endoderm. Cubilin-deficient VE is also functionally defective, unable to mediate uptake of maternally derived high-density lipoprotein (HDL). Conclusion: In summary, cubilin is required for embryonic development and is essential for the formation of somites, definitive endoderm and VE and for the absorptive function of VE including the process of maternal-embryo transport of HDL.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Targeted disruption of megalin and cubilin leads to failure of somite formation, indicating their key role in supporting early embryogenesis.
“Targeted disruption of these receptors leads to failure of somite formation, indicating their key role in supporting early embryogenesis (506).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [506]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Organoid Models and Applications in Biomedical Research
Xinaris, C., Brizi, V., & Remuzzi, G. (2015) · The Nephron journals/Nephron journals · doi:10.1159/000433566 · Cited by 3,517 · see citing works
Embryonic retinoic acid synthesis is essential for early mouse post-implantation development
Niederreither, K., Subbarayan, V., Dollé, P., & Chambon, P. (1999) · Nature Genetics · doi:10.1038/7788 · Cited by 1,111 · see citing works
Megalin and cubilin: multifunctional endocytic receptors
Christensen, E., & Birn, H. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm778 · Cited by 829 · see citing works
Defective forebrain development in mice lacking gp330/megalin.
Willnow, T. E., Hilpert, J., Armstrong, S. A., Rohlmann, A., Hammer, R. E., Burns, D. K., & Herz, J. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.16.8460 · Cited by 482 · see citing works
Vasculogenesis in the day 6.5 to 9.5 mouse embryo
Drake, C. J., & Fleming, P. A. (2000) · Blood · doi:10.1182/blood.v95.5.1671.005k39_1671_1679 · Cited by 453 · see citing works
Self-citationFyfe, J. C., Madsen, M. M., Højrup, P., Christensen, E., Tanner, S. M., de la Chapelle, A., He, Q., & Moestrup, S. K. (2003) · Blood · doi:10.1182/blood-2003-08-2852 · Cited by 307 · see citing works
Kozyraki, R., Fyfe, J. C., Kristiansen, M., Gerdes, C., Jacobsen, C. B., Cui, S., Christensen, E., Aminoff, M., de la Chapelle, A., Krahe, R., et al. (1999) · Nature Medicine · doi:10.1038/9504 · Cited by 273 · see citing works
Hem, A., Smith, A. J., & Solberg, P. (1998) · Laboratory Animals · doi:10.1258/002367798780599866 · Cited by 265 · see citing works
Moestrup, S. K., Kozyraki, R., Kristiansen, M., et al. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.9.5235 · Cited by 258 · see citing works
Woollett, L. A. (2005) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/82.6.1155 · Cited by 205 · see citing works
Sirbu, I. O., & Duester, G. (2006) · Nature Cell Biology · doi:10.1038/ncb1374 · Cited by 171 · see citing works
Kozyraki, R., Kristiansen, M., Silahtaroglu, A., et al. (1998) · Blood · doi:10.1182/blood.v91.10.3593 · Cited by 167 · see citing works
Yang, D., Smith, E. R., Roland, I. H., Sheng, Z., He, J., Martin, W. D., Hamilton, T. C., Lambeth, J. D., & Xu, X. (2002) · Developmental Biology · doi:10.1006/dbio.2002.0810 · Cited by 167 · see citing works
Definitive endoderm of the mouse embryo: Formation, cell fates, and morphogenetic function
Lewis, S. L., & Tam, P. P. L. (2006) · Developmental Dynamics · doi:10.1002/dvdy.20846 · Cited by 164 · see citing works
Hammad, S. M., Stefansson, S., Twal, W. O., Drake, C. J., Fleming, P., Remaley, A. T., Brewer, H. B., & Argraves, W. S. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.18.10158 · Cited by 156 · see citing works
Self-citationTanner, S. M., Aminoff, M., Wright, F. A., et al. (2003) · Nature Genetics · doi:10.1038/ng1098 · Cited by 151 · see citing works
Farese, R. V., Cases, S., Ruland, S. L., et al. (1996) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)37621-5 · Cited by 150 · see citing works
Megalin Acts in Concert with Cubilin to Mediate Endocytosis of High Density Lipoproteins
Hammad, S. M., Barth, J. L., Knaak, C., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.16.12003 · Cited by 148 · see citing works
Self-citationSahali, D., Mulliez, N., Chatelet, F.-P., et al. (1988) · The Journal of Experimental Medicine · doi:10.1084/jem.167.1.213 · Cited by 136 · see citing works
Kristiansen, M., Kozyraki, R., Jacobsen, C. B., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.29.20540 · Cited by 132 · see citing works
Seetharam, B., Christensen, E., Moestrup, S. K., et al. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119411 · Cited by 121 · see citing works
Endocytosis of megalin by visceral endoderm cells requires the Dab2 adaptor protein
Maurer, M. E., & Cooper, J. A. (2005) · Journal of Cell Science · doi:10.1242/jcs.02650 · Cited by 104 · see citing works
Coudroy, G. D., Gburek, J., Kozyraki, R., et al. (2005) · Journal of the American Society of Nephrology · doi:10.1681/asn.2004110925 · Cited by 96 · see citing works
Receptor-mediated transport of cholesterol between cultured cells and high-density lipoproteins
Oram, J. F. (1986) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(86)29096-5 · Cited by 92 · see citing works
Strope, S., Rivi, R., Metzger, T. E., Manova, K., & Lacy, E. (2004) · Development · doi:10.1242/dev.01341 · Cited by 84 · see citing works
Cubilin and Megalin Partners in Lipoprotein and Vitamin Metabolism
Barth, J. L. (2001) · Trends in Cardiovascular Medicine · doi:10.1016/s1050-1738(01)00080-9 · Cited by 67 · see citing works
Self-citationAssémat, E., Vinot, S., Gofflot, F., et al. (2004) · Biology of Reproduction · doi:10.1095/biolreprod.104.036913 · Cited by 62 · see citing works
Tomihara-Newberger, C., Haub, O., Lee, H.-G., Soares, V., Manova, K., & Lacy, E. (1998) · Developmental Biology · doi:10.1006/dbio.1998.9034 · Cited by 48 · see citing works
Identification and Characterization of Two Distinct Ligand Binding Regions of Cubilin
Yammani, R. R., Seetharam, S., Seetharam, B., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106419200 · Cited by 45 · see citing works
Apolipoprotein expression by murine visceral yolk sac endoderm
Shi, W.-K., & Heath, J. K. (1984) · Development · doi:10.1242/dev.81.1.143 · Cited by 44 · see citing works
VEGF signaling is required for the assembly but not the maintenance of embryonic blood vessels
Argraves, W. S., LaRue, A. C., Fleming, P. A., & Drake, C. J. (2002) · Developmental Dynamics · doi:10.1002/dvdy.10162 · Cited by 40 · see citing works
Self-citationSahali, D., Mulliez, N., Chatelet, F.-P., et al. (1992) · PubMed · Cited by 37 · see citing works
Differential distribution of cubilin and megalin expression in the mouse embryo
Drake, C. J., Fleming, P. A., LaRue, A. C., Barth, J. L., Chintalapudi, M. R., & Argraves, W. S. (2004) · The Anatomical Record Part A Discoveries in Molecular Cellular and Evolutionary Biology · doi:10.1002/ar.a.10123 · Cited by 34 · see citing works
Self-citationYammani, R. R., Sharma, M., Seetharam, S., et al. (2002) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00752.2001 · Cited by 26 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Placental Origins of Chronic Disease
Burton, G. J., Fowden, A. L., & Thornburg, K. L. (2016) · Physiological Reviews · doi:10.1152/physrev.00029.2015 · Cited by 717 · see citing works
Artus, J., Douvaras, P., Piliszek, A., Isern, J., Baron, M. H., & Hadjantonakis, A.-K. (2012) · Developmental Biology · doi:10.1016/j.ydbio.2011.10.015 · Cited by 83 · see citing works
- Authors
- Smith, B. T., Mussell, J. C., Fleming, P. A., Barth, J. L., Spyropoulos, D. D., Cooley, M. A., Drake, C. J., & Argraves, W. S.
- Affiliations
- Medical University of South Carolina (US)
- Corresponding author
- Argraves, W Scott
- Venue
- BMC Developmental Biology
- Published
- 2006-06-20
- Volume
- 6
- Issue
- 1
- Pages
- 30-30
- ISSN
- 1471-213X (ISSN-L)
- OpenAlex
- W1519282881
- Cited by
- 66
- References
- 35
- Citations by year
- 2023: 1 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 4 · 2018: 4 · 2017: 3 · 2016: 5 · 2015: 2 · 2014: 3 · 2013: 10 · 2012: 7
- FWCI
- 1.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- BMC Developmental Biology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- U.S. Department of Defense (HL07260)
- Medical University of South Carolina
- National Institutes of Health (5r03ca109958-02)
- National Heart, Lung, and Blood Institute (T32-HL-07260, R01HL057375, HL061873, HL 57375, T32HL007260, R01HL061873, T32HL007710)
- National Cancer Institute (CA109958, R03 CA109958)
- National Institute of Dental and Craniofacial Research (DE14347, R01DE014347)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Renal and related cancers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Keywords
- cubilin, megalin, amnionless, visceral endoderm, definitive endoderm, somitogenesis, embryonic lethality, yolk sac blood islands, HDL uptake, endocytosis, mouse embryo, mesoderm formation
- MeSH terms
- Animals, Embryo, Mammalian, Endoderm, Exons, Genes, Lethal, Lipoproteins, HDL, Mesoderm, Receptors, Cell Surface, Yolk Sac, Sequence Deletion, Mice, Knockout, Somites, 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
