Lrp4 regulates initiation of ureteric budding and is crucial for kidney formation – a mouse model for Cenani–Lenz syndrome
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BACKGROUND: Development of the kidney is initiated when the ureteric bud (UB) branches from the Wolffian duct and invades the overlying metanephric mesenchyme (MM) triggering the mesenchymal/epithelial interactions that are the basis of organ formation. Multiple signaling pathways must be integrated to ensure proper timing and location of the ureteric bud formation. METHODS AND PRINCIPAL FINDINGS: We have used gene targeting to create an Lrp4 null mouse line. The mutation results in early embryonic lethality with a subpenetrant phenotype of kidney agenesis. Ureteric budding is delayed with a failure to stimulate the metanephric mesenchyme in a timely manner, resulting in failure of cellular differentiation and resulting absence of kidney formation in the mouse as well as comparable malformations in humans with Cenani-Lenz syndrome. CONCLUSION: Lrp4 is a multi-functional receptor implicated in the regulation of several molecular pathways, including Wnt and Bmp signaling. Lrp4(-/-) mice show a delay in ureteric bud formation that results in unilateral or bilateral kidney agenesis. These data indicate that Lrp4 is a critical regulator of UB branching and lack of Lrp4 results in congenital kidney malformations in humans and mice.
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Lrp4 is the gene mutated in Cenani-Lenz syndrome.
“Lrp4 is more commonly known as the gene defective in Cenani-Lenz syndrome [83–86]”
From ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease (2017) · cites this paper as [83]
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Intestinal polyposis in mice with a dominant stable mutation of the β‐catenin gene
Harada, N., Tamai, Y., Ishikawa, T., Sauer, B., Takaku, K., Oshima, M., & Taketo, M. M. (1999) · The EMBO Journal · doi:10.1093/emboj/18.21.5931 · Cited by 1,198 · see citing works
Carroll, T. J., Park, J., Hayashi, S., Majumdar, Å., & McMahon, A. P. (2005) · Developmental Cell · doi:10.1016/j.devcel.2005.05.016 · Cited by 903 · see citing works
Self-citationMajumdar, Å., Vainio, S. J., Kispert, A., McMahon, J. A., & McMahon, A. P. (2003) · Development · doi:10.1242/dev.00520 · Cited by 475 · see citing works
Favor, J., Sandulache, R., Neuhäuser-Klaus, A., Pretsch, W., Chatterjee, B., Senft, E., Wurst, W., Blanquet, V., Grimes, P. A., Spörle, R., et al. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.13870 · Cited by 391 · see citing works
Early organogenesis of the kidney
Sax�n, L., & Sariola, H. V. (1987) · Pediatric Nephrology · doi:10.1007/bf00849241 · Cited by 368 · see citing works
LDL-receptor-related protein 4 is crucial for formation of the neuromuscular junction
Weatherbee, S. D., Anderson, K. V., & Niswander, L. A. (2006) · Development · doi:10.1242/dev.02696 · Cited by 351 · see citing works
GDNF/Ret signaling and the development of the kidney
Costantini, F. D., & Shakya, R. (2006) · BioEssays · doi:10.1002/bies.20357 · Cited by 328 · see citing works
Proteoglycans are required for maintenance of Wnt-11 expression in the ureter tips
Kispert, A., Vainio, S. J., Shen, L., Rowitch, D. H., & McMahon, A. P. (1996) · Development · doi:10.1242/dev.122.11.3627 · Cited by 306 · see citing works
Deregulation of Pax-2 expression in transgenic mice generates severe kidney abnormalities
Dressler, G. R., Wilkinson, J. E., Rothenpieler, U. W., et al. (1993) · Nature · doi:10.1038/362065a0 · Cited by 289 · see citing works
Pax-2 is required for mesenchyme-to-epithelium conversion during kidney development
Rothenpieler, U. W., & Dressler, G. R. (1993) · Development · doi:10.1242/dev.119.3.711 · Cited by 275 · see citing works
Klotho as a regulator of fibroblast growth factor signaling and phosphate/calcium metabolism
Kuro‐o, M. (2006) · Current Opinion in Nephrology & Hypertension · doi:10.1097/01.mnh.0000232885.81142.83 · Cited by 246 · see citing works
Michos, O., Gonçalves, A., López-Rı́os, J., et al. (2007) · Development · doi:10.1242/dev.02861 · Cited by 216 · see citing works
Chromosome maps of man and mouse. IV
Searle, A. G., Peters, J., Lyon, M. F., Hall, J. G., Evans, E. P., Edwards, J. H., & Buckle, V. J. (1989) · Annals of Human Genetics · doi:10.1111/j.1469-1809.1989.tb01777.x · Cited by 213 · see citing works
Choi, H. Y., Dieckmann, M., Herz, J., & Niemeier, A. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007930 · Cited by 206 · see citing works
Self-citationLrp4 Modulates Extracellular Integration of Cell Signaling Pathways in Development
Ohazama, A., Johnson, E. B., Ota, M. S., Choi, H. J., Porntaveetus, T., Oommen, S., Itoh, N., Eto, K., Gritli-Linde, A., Herz, J., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0004092 · Cited by 196 · see citing works
Self-citationLi, Y., Pawlik, B., Elcioglu, N., Aglan, M., Kayserili, H., Yigit, G., Percin, F., Goodman, F., Nürnberg, G., Cenani, A., et al. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.03.004 · Cited by 171 · see citing works
Self-citationAbnormal development of the apical ectodermal ridge and polysyndactyly in Megf7-deficient mice
Johnson, E. B., Hammer, R. E., & Herz, J. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi381 · Cited by 141 · see citing works
Self-citationMolecular regulation of kidney development: is the answer blowing in the Wnt?
Merkel, C. E., Karner, C. M., & Carroll, T. J. (2007) · Pediatric Nephrology · doi:10.1007/s00467-007-0504-4 · Cited by 89 · see citing works
Self-citationThe role of GDNF in patterning the excretory system.
Shakya, R., Jho, E., Kotka, P., Wu, Z.-Q., Kholodilov, N., Burke, R. E., D'Agati, V., & Costantini, F. (2005) · Developmental Biology · doi:10.1016/j.ydbio.2005.04.008 · Cited by 88 · see citing works
Molecular development of the kidney: A review of the results of gene disruption studies
Lipschutz, J. H. (1998) · American Journal of Kidney Diseases · doi:10.1053/ajkd.1998.v31.pm9506676 · Cited by 87 · see citing works
Chromosome maps of man and mouse
Dalton, T. P., Edwards, J. H., Evans, E. P., et al. (1981) · Clinical Genetics · doi:10.1111/j.1399-0004.1981.tb01050.x · Cited by 87 · see citing works
Comparative Mechanisms of Branching Morphogenesis in Diverse Systems
Lu, P., Sternlicht, M. D., & Werb, Z. (2006) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-006-9027-z · Cited by 79 · see citing works
THE MORPHOLOGICAL MANIFESTATIONS OF A DOMINANT MUTATION IN MICE AFFECTING TAIL AND UROGENITAL SYSTEM
Gluecksohn‐Schoenheimer, S. (1943) · Genetics · doi:10.1093/genetics/28.4.341 · Cited by 78 · see citing works
THE EMBRYONIC DEVELOPMENT OF MUTANTS OF THE Sd-STRAIN IN MICE
Gluecksohn‐Schoenheimer, S. (1945) · Genetics · doi:10.1093/genetics/30.1.29 · Cited by 77 · see citing works
An in vivo reporter of BMP signaling in organogenesis reveals targets in the developing kidney
Blank, U., Seto, M. L., Adams, D. C., et al. (2008) · BMC Developmental Biology · doi:10.1186/1471-213x-8-86 · Cited by 65 · see citing works
Johnson, E. B., Steffen, D. J., Lynch, K. W., & Herz, J. (2006) · Genomics · doi:10.1016/j.ygeno.2006.08.005 · Cited by 62 · see citing works
Self-citationMaas, R. L., Elfering, S., Glaser, T. M., et al. (1994) · Developmental Dynamics · doi:10.1002/aja.1001990306 · Cited by 58 · see citing works
Tomita, Y., Kim, D. H., Magoori, K., Fujino, T., & Yamamoto, T. (1998) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a022180 · Cited by 53 · see citing works
Aberrant Expression of Pax-2 in Danforth's Short Tail (Sd) Mice
Phelps, D. E., & Dressler, G. R. (1993) · Developmental Biology · doi:10.1006/dbio.1993.1129 · Cited by 39 · see citing works
Stimulatory and inhibitory signaling molecules that regulate renal branching morphogenesis
Bridgewater, D. J., & Rosenblum, N. D. (2008) · Pediatric Nephrology · doi:10.1007/s00467-008-1048-y · Cited by 36 · see citing works
Sampogna, R. V., & Nigám, S. K. (2004) · Physiology · doi:10.1152/physiol.00025.2004 · Cited by 35 · see citing works
Kidney Development: Regulatory Molecules Crucial to Both Mice and Men
Bates, C. M. (2000) · Molecular Genetics and Metabolism · doi:10.1006/mgme.2000.3072 · Cited by 29 · see citing works
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- Authors
- Karner, C. M., Dietrich, M. F., Johnson, E. B., Kappesser, N., Tennert, C., Percin, F., Wollnik, B., Carroll, T. J., & Herz, J.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- University of Cologne (DE)
- Corresponding author
- Herz, Joachim
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-04-29
- Volume
- 5
- Issue
- 4
- Pages
- e10418
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2861670
- OpenAlex
- W2004818856
- Cited by
- 57
- References
- 32
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 5 · 2022: 2 · 2021: 4 · 2020: 3 · 2019: 1 · 2018: 6 · 2017: 7 · 2016: 2 · 2015: 4 · 2014: 6 · 2013: 8 · 2012: 2
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- GRO (submittedVersion)
- Funders
- American Health Assistance Foundation
- E-Rare
- Bundesministerium für Bildung und Forschung (01GM0880, 01GM0801)
- Boehringer Ingelheim Stiftung
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R37HL063762)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Renal and related cancers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Urology › Urological Disorders and Treatments
- Keywords
- LRP4, ureteric bud, kidney development, metanephric mesenchyme, renal agenesis, congenital kidney anomaly, epithelial-mesenchymal interactions, Wnt signaling, BMP signaling, embryonic lethality
- MeSH terms
- Animals, Cell Differentiation, Disease Models, Animal, Humans, Kidney, Kidney Diseases, Mesoderm, Receptors, LDL, Syndrome, Ureter, Signal Transduction, Mice, Knockout, LDL-Receptor Related Proteins, Mice
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