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Relationship: 2082
Title
Increase, Cripto-1 expression leads to Inhibition, Fin regeneration
Upstream event
Downstream event
Key Event Relationship Overview
AOPs Referencing Relationship
AOP Name | Adjacency | Weight of Evidence | Quantitative Understanding | Point of Contact | Author Status | OECD Status |
---|---|---|---|---|---|---|
Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration | non-adjacent | Moderate | Alexander Cole (send email) | Open for citation & comment |
Taxonomic Applicability
Term | Scientific Term | Evidence | Link |
---|---|---|---|
teleost fish | teleost fish | Moderate | NCBI |
Sex Applicability
Sex | Evidence |
---|---|
Mixed | Moderate |
Life Stage Applicability
Term | Evidence |
---|---|
All life stages | Moderate |
Key Event Relationship Description
Cripto-1 is responsible for growth factor activity, as well as activin binding on the cell membrane. Cripto-1 may also be referred to as teratocarcinoma-derived growth factor 1, tdgf1, or one-eyed pinhead protein, depending on the species (Uniprot). Cripto-1 is a known activin inhibitor (Garland et al., 2019).
Uniprot ID
Fin regeneration is a naturally occurring process in fish (Fu et al., 2013). Fin regeneration is a complex process involving coordinated cellular processes such as cellular signaling, differentiation, and migration (Wehner & Weidinger, 2015). Commonly known signaling pathways such as activin signaling, notch signaling and wnt signaling all play a role in the process of fin regeneration (Wehner & Weidinger, 2015).
An increase in cripto-1 will disrupt pathways involved with fin regeneration resulting in an impairment to the regeneration process.
Evidence Collection Strategy
Evidence Supporting this KER
Biological Plausibility
- Cripto-1 is a known activin inhibitor (Garland et al., 2019).
- Activin signalling is crucial to cell migration in the fin regeneration process (Wehner & Weidinger, 2015).
- Cripto-1's ability to inhibit activin signalling would cause an impairment in the fin regeneration process.
Empirical Evidence
Larval zebrafish exposed to GR agonists show increased levels of cripto-1 transcripts. Fish with elevated levels of cripto-1 also experience impaired fin regeneration compared to a control fish (Sengupta et al, 2012; Garland et al., 2019).
Uncertainties and Inconsistencies
This relationship has only been observed in larval zebrafish.
Known modulating factors
Not yet evaluated.
Quantitative Understanding of the Linkage
Not yet evaluated.
Response-response Relationship
Not yet evaluated.
Time-scale
Not yet evaluated.
Known Feedforward/Feedback loops influencing this KER
Not yet evaluated.
Domain of Applicability
- The EGF and CFC regions of the protein are highly conserved cross species and provide similar function. However there is fuctional differentiation in mammals compared to that of other species (Ravisankar et al., 2011).
- Fin regeneration has been observed in many species including the qingbo (Spinibarbus sinensis), the common carp (Cyprinus carpio) the goldfish (Carassius auratus; Fu et al., 2013), zebrafish (Danio rerio; Sengupta et al., 2012) and fathead minnow (Pimephales promelas), allowing the inferral of fin regeneration being universal to all ray-finned fish (teleost).
References
Fu C, Cao ZD, Fu SJ. 2013. The effects of caudal fin loss and regeneration on the swimming performance of three cyprinid fish species with different swimming capacities. The Journal of Experimental Biology 216:3164-3174. doi:10.1242/jeb.084244
Garland MA, Sengupta S, Mathew LK, Truong L, Jong ED, Piersma AH, Du JL, Tanguay RL. 2019. Glucocorticoid receptor-dependent induction of cripto-1 (one-eyed pinhead) inhibits zebrafish caudal fin regeneration. Toxicology Reports 6:529-537.
Ravisankar V, Signh TP, Manoj N. 2011. Molecular evolution of the EGF-CFC protein family. Gene, 428:43-50. doi:10.1016/j.gene.2011.05.007
Sengupta S, Bisson WH, Mathew LK, Kolluri SK, Tanguay RL. 2012. Alternative glucocorticoid receptor ligand binding structures influence outcomes in an in vivo tissue regeneration model. Comparative Biochemistry and Physiology, Part C 156:121-129.
Wehner D, Weidinger G. 2015. Signaling networks organizing regenerative growth of the zebrafish fin. Trends in Genetics 31 (6):336-343. http://dx.doi.org/10.1016/j.tig.2015.03.012