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Research Resource: Comprehensive Expression Atlas of the Fibroblast Growth Factor System in Adult Mouse
Open accessAbstract
Although members of the fibroblast growth factor (FGF) family and their receptors have well-established roles in embryogenesis, their contributions to adult physiology remain relatively unexplored. Here, we use real-time quantitative PCR to determine the mRNA expression patterns of all 22 FGFs, the seven principal FGF receptors (FGFRs), and the three members of the Klotho family of coreceptors in 39 different mouse tissues. Unsupervised hierarchical cluster analysis of the mRNA expression data reveals that most FGFs and FGFRs fall into two groups the expression of which is enriched in either the central nervous system or reproductive and gastrointestinal tissues. Interestingly, the FGFs that can act as endocrine hormones, including FGF15/19, FGF21, and FGF23, cluster in a third group that does not include any FGFRs, underscoring their roles in signaling between tissues. We further show that the most recently identified Klotho family member, Lactase-like, is highly and selectively expressed in brown adipose tissue and eye and can function as an additional coreceptor for FGF19. This FGF atlas provides an important resource for guiding future studies to elucidate the physiological functions of FGFs in adult animals.
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“KLB expression is primarily restricted to specific metabolic tissues (for example, the liver, pancreas and adipose tissue)5, and lower expression is observed in the brain22,48–50. Despite some reports to the contrary51,52, KLB is not expressed in muscle5,41.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [5]
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“FGF21, unlike traditional FGFs, is an endocrine hormone produced and secreted predominantly by the liver [129,130].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [130]
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Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837
Self-citationFGF-21 as a novel metabolic regulator
Kharitonenkov, A., Shiyanova, T. L., Koester, A., Ford, A. M., Micanovic, R., Galbreath, E. J., Sandusky, G. E., Hammond, L. J., Moyers, J. S., Owens, R. A., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23606 · Cited by 2,125
Suppression of Aging in Mice by the Hormone Klotho
Kurosu, H., Yamamoto, M., Clark, J. D., Pastor, J. V., Nandi, A., Gurnani, P., McGuinness, O. P., Chikuda, H., Yamaguchi, M., Kawaguchi, H., et al. (2005) · Science · doi:10.1126/science.1112766 · Cited by 1,935
Self-citationFibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis
Inagaki, T., Choi, M., Moschetta, A., Peng, L., Cummins, C. L., McDonald, J. G., Luo, G., Jones, S. A., Goodwin, B., Richardson, J. A., et al. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.09.001 · Cited by 1,865
Self-citationKlotho converts canonical FGF receptor into a specific receptor for FGF23
Urakawa, I., Yamazaki, Y., Shimada, T., Iijima, K., Hasegawa, H., Okawa, K., Fujita, T., Fukumoto, S., & Yamashita, T. (2006) · Nature · doi:10.1038/nature05315 · Cited by 1,865
Inagaki, T., Dutchak, P., Zhao, G., Ding, X., Gautron, L., Parameswara, V., Li, Y., Goetz, R., Mohammadi, M., Esser, V., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.003 · Cited by 1,504
Self-citationShimada, T., Kakitani, M., Yamazaki, Y., Hasegawa, H., Takeuchi, Y., Fujita, T., Fukumoto, S., Tomizuka, K., & Yamashita, T. (2004) · Journal of Clinical Investigation · doi:10.1172/jci19081 · Cited by 1,503
Badman, M. K., Pissios, P., Kennedy, A. R., Koukos, G., Flier, J. S., & Maratos-Flier, E. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.002 · Cited by 1,495
Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia
Shimada, T., Mizutani, S., Muto, T., Yoneya, T., Hino, R., Takeda, S., Takeuchi, Y., Fujita, T., Fukumoto, S., & Yamashita, T. (2001) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.101545198 · Cited by 1,391
Regulation of Fibroblast Growth Factor-23 Signaling by Klotho
Kurosu, H., Ogawa, Y., Miyoshi, M., Yamamoto, M., Nandi, A., Rosenblatt, K. P., Baum, M. G., Schiavi, S. C., Hu, M. C., Moe, O. W., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.c500457200 · Cited by 1,381
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The Fibroblast Growth Factor signaling pathway
Ornitz, D. M., & Itoh, N. (2015) · WIREs Developmental Biology · doi:10.1002/wdev.176 · Cited by 2,050
Chait, A., & den Hartigh, L. J. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00022 · Cited by 1,529
Bispecific antibodies: a mechanistic review of the pipeline
Labrijn, A. F., Janmaat, M. L., Reichert, J. M., & Parren, P. W. H. I. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0028-1 · Cited by 1,303
FGF/FGFR signaling in health and disease
Xie, Y., Su, N., Yang, J., Tan, Q., Huang, S., Jin, M., Ni, Z., Zhang, B., Zhang, D., Luo, F., et al. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00222-7 · Cited by 904
Gut-liver axis: Pathophysiological concepts and clinical implications
Tilg, H., Adolph, T. E., & Trauner, M. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.09.017 · Cited by 843
Metadata
- Authors
- Fon Tacer, K., Bookout, A. L., Ding, X., Kurosu, H., John, G. B., Wang, L., Goetz, R., Mohammadi, M., Kuro-o, M., Mangelsdorf, D. J., & Kliewer, S. A.
- Affiliations
- Department of Molecular Biology (K.F.T., X.D., S.A.K.), Dallas, Texas 75390
- Howard Hughes Medical Institute (US)
- Department of Pathology (H.K., G.B.J., L.W., M.K.), Dallas, Texas 75390
- New York University (US)
- Corresponding author
- Mangelsdorf, David J.
- Kliewer, Steven A.
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2010-10-01
- Volume
- 24
- Issue
- 10
- Pages
- 2050-2064
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- PMC
- PMC2954642
- OpenAlex
- W1968091833
- Cited by
- 700
- References
- 116
- Citations by year
- 2026: 22 · 2025: 38 · 2024: 46 · 2023: 48 · 2022: 53 · 2021: 68 · 2020: 52 · 2019: 64 · 2018: 55 · 2017: 41 · 2016: 45 · 2015: 53 · 2014: 28 · 2013: 32 · 2012: 35
- FWCI
- 11.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Endocrinology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute (I-1558, I-1275)
- Welch Foundation (I-1275, I-1558, GM007062)
- National Institutes of Health (I-1275, I-1558, DK067158, U19DK62434, AG19712)
- National Institute on Aging (AG-19712, R01AG019712)
- National Institute of General Medical Sciences (T32GM007062, GM007062, RL1GM084436)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-067158, U19 DK-62434, U19DK062434, R01DK067158)
- National Institute of Dental and Craniofacial Research (DE13686, R01DE013686)
- National Center for Research Resources (P20RR20691, P20RR020691)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
- Keywords
- fibroblast growth factor, fibroblast growth factor receptor, FGF19, FGF21, fibroblast growth factor 23, FGF15/19, tissue-specific gene expression, adult mice, brown adipose tissue, hormone signaling, central nervous system
- MeSH terms
- Fibroblast Growth Factor-23, Animals, Atlases as Topic, Fibroblast Growth Factors, Humans, Mice, Inbred C57BL, RNA, Messenger, Tissue Distribution, Cluster Analysis, Receptors, Fibroblast Growth Factor, Gene Expression Profiling, Microarray Analysis, Mice
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