The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
Notch signaling controls liver development by regulating biliary differentiation
Open accessAbstract
In the mammalian liver, bile is transported to the intestine through an intricate network of bile ducts. Notch signaling is required for normal duct formation, but its mode of action has been unclear. Here, we show in mice that bile ducts arise through a novel mechanism of tubulogenesis involving sequential radial differentiation. Notch signaling is activated in a subset of liver progenitor cells fated to become ductal cells, and pathway activation is necessary for biliary fate. Notch signals are also required for bile duct morphogenesis, and activation of Notch signaling in the hepatic lobule promotes ectopic biliary differentiation and tubule formation in a dose-dependent manner. Remarkably, activation of Notch signaling in postnatal hepatocytes causes them to adopt a biliary fate through a process of reprogramming that recapitulates normal bile duct development. These results reconcile previous conflicting reports about the role of Notch during liver development and suggest that Notch acts by coordinating biliary differentiation and morphogenesis.
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Cites
Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1
Li, L., Krantz, I. D., Deng, Y., Genin, A., Banta, A. B., Collins, C. C., Qi, M., Trask, B. J., Kuo, W. L., Cochran, J., et al. (1997) · Nature Genetics · doi:10.1038/ng0797-243 · Cited by 1,284
Mutations in the human Jagged1 gene are responsible for Alagille syndrome
Oda, T., Elkahloun, A. G., Pike, B. L., Okajima, K., Krantz, I. D., Genin, A., Piccoli, D. A., Meltzer, P. S., Spinner, N. B., Collins, F. S., et al. (1997) · Nature Genetics · doi:10.1038/ng0797-235 · Cited by 1,158
Advances in Male Contraception
Page, S. T., Amory, J. K., & Bremner, W. J. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0041 · Cited by 1,134
Timmerman, L. A., Grego-Bessa, J., Raya, A., Bertrán, E., Pérez-Pomares, J. M., Díez, J., Aranda, S., Palomo, S., McCormick, F., Izpisúa-Belmonte, J. C., et al. (2004) · Genes & Development · doi:10.1101/gad.276304 · Cited by 985
Notch signaling controls multiple steps of pancreatic differentiation
Murtaugh, L. C., Stanger, B. Z., Kwan, K. M., & Melton, D. A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2436557100 · Cited by 782
Self-citationNOTCH2 Mutations Cause Alagille Syndrome, a Heterogeneous Disorder of the Notch Signaling Pathway
McDaniell, R., Warthen, D. M., Sanchez-Lara, P. A., Pai, A., Krantz, I. D., Piccoli, D. A., & Spinner, N. B. (2006) · The American Journal of Human Genetics · doi:10.1086/505332 · Cited by 749
Alagille, D., Estrada, A., Hadchouel, M., Gautler, M., Odièvre, M., & Dommergues, J. P. (1987) · The Journal of Pediatrics · doi:10.1016/s0022-3476(87)80153-1 · Cited by 662
Lubarsky, B., & Krasnow, M. A. (2003) · Cell · doi:10.1016/s0092-8674(02)01283-7 · Cited by 660
Features of Alagille Syndrome in 92 Patients: Frequency and Relation to Prognosis
Emerick, K. M., Rand, E. B., Goldmuntz, E., Krantz, I. D., Spinner, N. B., & Piccoli, D. A. (1999) · Hepatology · doi:10.1002/hep.510290331 · Cited by 660
The Hes gene family: repressors and oscillators that orchestrate embryogenesis
Kageyama, R., Ohtsuka, T., & Kobayashi, T. (2007) · Development · doi:10.1242/dev.000786 · Cited by 644
Cited by
EMT and Dissemination Precede Pancreatic Tumor Formation
Rhim, A. D., Mirek, E. T., Aiello, N. M., Maitra, A., Bailey, J. M., McAllister, F., Reichert, M., Beatty, G. L., Rustgi, A. K., Vonderheide, R. H., et al. (2012) · Cell · doi:10.1016/j.cell.2011.11.025 · Cited by 2,136
Self-citationNotch signaling: simplicity in design, versatility in function
Andersson, E. R., Sandberg, R., & Lendahl, U. (2011) · Development · doi:10.1242/dev.063610 · Cited by 950
Hippo Pathway Activity Influences Liver Cell Fate
Yimlamai, D., Christodoulou, C., Galli, G. G., Yanger, K., Pepe-Mooney, B., Gurung, B., Shrestha, K., Cahan, P., Stanger, B. Z., & Camargo, F. D. (2014) · Cell · doi:10.1016/j.cell.2014.03.060 · Cited by 857
Self-citationZhang, N., Bai, H., David, K. K., Dong, J., Zheng, Y., Cai, J., Giovannini, M., Liu, P., Anders, R. A., & Pan, D. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.06.015 · Cited by 804
Organogenesis and development of the liver
Si-Tayeb, K., Lemaigre, F. P., & Duncan, S. A. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.01.011 · Cited by 800
Self-citationHepatic stellate cells in liver development, regeneration, and cancer
Yin, C., Evason, K. J., Asahina, K., & Stainier, D. Y. R. (2013) · Journal of Clinical Investigation · doi:10.1172/jci66369 · Cited by 719
Kopp, J. L., von Figura, G., Mayes, E., Liu, F.-F., Dubois, C. L., Morris, J. P., Pan, F. C., Akiyama, H., Wright, C. V. E., Jensen, K., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.10.025 · Cited by 697
Stem/progenitor cells in liver development, homeostasis, regeneration, and reprogramming
Miyajima, A., Tanaka, M., & Itoh, T. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.04.010 · Cited by 570
Cholangiocarcinomas can originate from hepatocytes in mice
Fan, B., Malato, Y., Calvisi, D. F., Naqvi, S., Razumilava, N., Ribback, S., Gores, G. J., Dombrowski, F., Evert, M., Chen, X., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci63212 · Cited by 529
The roles of signaling pathways in bone repair and regeneration
Majidinia, M., Sadeghpour, A., & Yousefi, B. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.26042 · Cited by 513
Robust cellular reprogramming occurs spontaneously during liver regeneration
Yanger, K., Zong, Y., Maggs, L. R., Shapira, S. N., Maddipati, R., Aiello, N. M., Thung, S. N., Wells, R. G., Greenbaum, L. E., & Stanger, B. Z. (2013) · Genes & Development · doi:10.1101/gad.207803.112 · Cited by 484
Self-citationAdult Hepatocytes Are Generated by Self-Duplication Rather than Stem Cell Differentiation
Yanger, K., Knigin, D., Zong, Y., Maggs, L., Gu, G., Akiyama, H., Pikarsky, E., & Stanger, B. Z. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.06.003 · Cited by 426
Self-citationOrchestrating liver development
Gordillo, M., Evans, T., & Gouon-Evans, V. (2015) · Development · doi:10.1242/dev.114215 · Cited by 375
Adult cell plasticity in vivo: de-differentiation and transdifferentiation are back in style
Merrell, A. J., & Stanger, B. Z. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.24 · Cited by 369
Self-citationNotch signaling in human development and disease
Penton, A. L., Leonard, L. D., & Spinner, N. B. (2012) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2012.01.010 · Cited by 332
Notch Signaling Is Activated in Human Hepatocellular Carcinoma and Induces Tumor Formation in Mice
Villanueva, A., Alsinet, C., Yanger, K., Hoshida, Y., Zong, Y., Toffanin, S., Rodriguez–Carunchio, L., Solé, M., Thung, S., Stanger, B. Z., et al. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.09.002 · Cited by 318
Self-citationDe novo formation of the biliary system by TGFβ-mediated hepatocyte transdifferentiation
Schaub, J. R., Huppert, K. A., Kurial, S. N. T., Hsu, B. Y., Cast, A. E., Donnelly, B., Karns, R. A., Chen, F., Rezvani, M., Luu, H. Y., et al. (2018) · Nature · doi:10.1038/s41586-018-0075-5 · Cited by 289
Hepatocyte Notch activation induces liver fibrosis in nonalcoholic steatohepatitis
Zhu, C., Kim, K., Wang, X., Bartolome, A., Salomao, M., Dongiovanni, P., Meroni, M., Graham, M. J., Yates, K. P., Diehl, A. M., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aat0344 · Cited by 250
Cellular Homeostasis and Repair in the Mammalian Liver
Stanger, B. Z. (2015) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021113-170255 · Cited by 248
Self-citationHippo signaling interactions with Wnt/β-catenin and Notch signaling repress liver tumorigenesis
Kim, W., Khan, S. K., Gvozdenovic-Jeremic, J., Kim, Y., Dahlman, J., Kim, H., Park, O., Ishitani, T., Jho, E.-H., Gao, B., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci88486 · Cited by 244
Inhibition of Notch signaling ameliorates insulin resistance in a FoxO1-dependent manner
Pajvani, U. B., Shawber, C. J., Samuel, V. T., Birkenfeld, A. L., Shulman, G. I., Kitajewski, J., & Accili, D. (2011) · Nature Medicine · doi:10.1038/nm.2378 · Cited by 193
Possible roles of DLK1 in the Notch pathway during development and disease
Falix, F. A., Aronson, D. C., Lamers, W. H., & Gaemers, I. C. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.02.003 · Cited by 191
Lineage fate of ductular reactions in liver injury and carcinogenesis
Jörs, S., Jeliazkova, P., Ringelhan, M., Thalhammer, J., Dürl, S., Ferrer, J., Sander, M., Heikenwalder, M., Schmid, R. M., Siveke, J. T., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci78585 · Cited by 149
Epithelial Plasticity during Liver Injury and Regeneration
Gadd, V. L., Aleksieva, N., & Forbes, S. J. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2020.08.016 · Cited by 142
Bipotent transitional liver progenitor cells contribute to liver regeneration
Pu, W., Zhu, H., Zhang, M., Pikiolek, M., Ercan, C., Li, J., Huang, X., Han, X., Zhang, Z., Lv, Z., et al. (2023) · Nature Genetics · doi:10.1038/s41588-023-01335-9 · Cited by 138
Transcription factors SOX4 and SOX9 cooperatively control development of bile ducts
Poncy, A., Antoniou, A., Cordi, S., Pierreux, C. E., Jacquemin, P., & Lemaigre, F. P. (2015) · Developmental Biology · doi:10.1016/j.ydbio.2015.05.012 · Cited by 125
Self-citationMaladaptive regeneration - the reawakening of developmental pathways in NASH and fibrosis
Zhu, C., Tabas, I., Schwabe, R. F., & Pajvani, U. B. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-00365-6 · Cited by 112
Tanimizu, N., Nishikawa, Y., Ichinohe, N., Akiyama, H., & Mitaka, T. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.517243 · Cited by 105
Hyun, J., Sun, Z., Ahmadi, A. R., Bangru, S., Chembazhi, U. V., Du, K., Chen, T., Tsukamoto, H., Rusyn, I., Kalsotra, A., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci132691 · Cited by 76
Cordero-Espinoza, L., Dowbaj, A. M., Kohler, T. N., Strauss, B., Sarlidou, O., Belenguer, G., Pacini, C., Martins, N. P., Dobie, R., Wilson-Kanamori, J. R., et al. (2021) · Cell Stem Cell · doi:10.1016/j.stem.2021.07.002 · Cited by 74
“Given that Notch signaling is a well-known inducer of mature DC fate in hepatoblasts (Hofmann et al., 2010; Sparks et al., 2010; Zong et al., 2009) and adult hepatocytes (Jeliazkova et al.”
BackgroundEmerging Roles of DLK1 in the Stem Cell Niche and Cancer Stemness
Grassi, E. S., & Pietras, A. (2022) · Journal of Histochemistry & Cytochemistry · doi:10.1369/00221554211048951 · Cited by 55
Seth, A., Ye, J., Yu, N., Guez, F., Bedford, D. C., Neale, G. A., Cordi, S., Brindle, P. K., Lemaigre, F. P., Kaestner, K. H., et al. (2014) · Development · doi:10.1242/dev.099481 · Cited by 50
Self-citationFetal liver development and implications for liver disease pathogenesis
Lotto, J., Stephan, T. L., & Hoodless, P. A. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00775-2 · Cited by 47
Dynamic Transcriptional and Epigenetic Changes Drive Cellular Plasticity in the Liver
Merrell, A. J., Peng, T., Li, J., Sun, K., Li, B., Katsuda, T., Grompe, M., Tan, K., & Stanger, B. Z. (2021) · Hepatology · doi:10.1002/hep.31704 · Cited by 42
Self-citationSignalling pathways and transcriptional regulators orchestrating liver development and cancer
Campbell, S. A., Stephan, T. L., Lotto, J., Cullum, R., Drissler, S., & Hoodless, P. A. (2021) · Development · doi:10.1242/dev.199814 · Cited by 22
Brovold, M., Keller, D., Devarasetty, M., Dominijanni, A., Shirwaiker, R., & Soker, S. (2021) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10207 · Cited by 11
Metadata
- Authors
- Zong, Y., Panikkar, A., Xu, J., Antoniou, A., Raynaud, P., Lemaigre, F., & Stanger, B. Z.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2009-05-15
- Volume
- 136
- Issue
- 10
- Pages
- 1727-1739
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2105042695
- Cited by
- 444
- References
- 58
- FWCI
- 15.74
- Type
- journal article
- Language
- en
- Open access
- bronze
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