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Zebrafish IGF Genes: Gene Duplication, Conservation and Divergence, and Novel Roles in Midline and Notochord Development
Open accessAbstract
Insulin-like growth factors (IGFs) are key regulators of development, growth, and longevity. In most vertebrate species including humans, there is one IGF-1 gene and one IGF-2 gene. Here we report the identification and functional characterization of 4 distinct IGF genes (termed as igf-1a, -1b, -2a, and -2b) in zebrafish. These genes encode 4 structurally distinct and functional IGF peptides. IGF-1a and IGF-2a mRNAs were detected in multiple tissues in adult fish. IGF-1b mRNA was detected only in the gonad and IGF-2b mRNA only in the liver. Functional analysis showed that all 4 IGFs caused similar developmental defects but with different potencies. Many of these embryos had fully or partially duplicated notochords, suggesting that an excess of IGF signaling causes defects in the midline formation and an expansion of the notochord. IGF-2a, the most potent IGF, was analyzed in depth. IGF-2a expression caused defects in the midline formation and expansion of the notochord but it did not alter the anterior neural patterning. These results not only provide new insights into the functional conservation and divergence of the multiple igf genes but also reveal a novel role of IGF signaling in midline formation and notochord development in a vertebrate model.
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“We suspected human IGF-1 would act via zebrafish receptors because the mature peptide shares ~81% identity with that of zebrafish (Zou et al., 2009), including key residues important for receptor binding (Gauguin et al., 2008). Furthermore, human and zebrafish IGF-IR share over 80% similarity and key residues involved in ligand binding are preserved (Ayaso et al., 2002; Renteria et al., 2008).”
From Retinal injury, growth factors, and cytokines converge on β-catenin and pStat3 signaling to stimulate retina regeneration (2014) · cites this paper as Zou et al., 2009
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Metadata
- Authors
- Zou, S., Kamei, H., Modi, Z., & Duan, C.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Duan, Cunming
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-09-17
- Volume
- 4
- Issue
- 9
- Pages
- e7026
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2738950
- OpenAlex
- W1986850329
- Cited by
- 122
- References
- 64
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 7 · 2023: 2 · 2022: 7 · 2021: 8 · 2020: 8 · 2019: 8 · 2018: 6 · 2017: 6 · 2016: 7 · 2015: 10 · 2014: 5 · 2013: 14 · 2012: 9
- FWCI
- 4.30
- 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)
- Funders
- National Science Foundation (0110864)
- China Scholarship Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Keywords
- insulin-like growth factor, gene duplication, functional divergence, notochord development, IGF signaling, zebrafish, gonads, liver
- MeSH terms
- Animals, Brain, Cloning, Molecular, Neurons, Notochord, Phylogeny, RNA, Messenger, Somatomedins, Zebrafish, Signal Transduction, Open Reading Frames, In Situ Hybridization, Gene Expression Regulation, Developmental, Body Patterning, Gene Duplication
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