Agnès BOUTET
Vertebrate Kidney Regeneration
Vertebrate Kidney Regeneration
KEYWORDS: Kidney, post-embryonic renal stem cell
Development, regeneration, translation regulation
Catshark
Development, regeneration, translation regulation
Catshark
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Team: Translation, Cell Cycle and Development. Morales’s Lab.
Station Biologique Sorbonne Université – CNRS UMR 8227 Place Georges Teissier – CS 90074 29688 Roscoff cedex Email A.Boutet Webpage |
Nephrons are the functional units of the kidney. During embryogenesis they are derived from a pool of self-renewing progenitors that cease propagation and are terminally differentiated within few days after birth in mammals. Each kidney is made of thousands or millions of nephrons. In mammals, the number of nephrons is fixed at birth meaning that the depletion of the progenitor pool is a physiological process and that adult mammals cannot generate new nephrons. In contrast, new nephrons are continually added to the adult kidney of elasmobranchs (a subclass of Chondrichthyes or cartilaginous fish) and this process contributes to the lifelong kidney growth in this taxon (Hentschel 1991, Elger et al. 2003). Neonephrogenesis is also observed upon partial nephrectomy in the little skate (Elger et al. 2003) indicating that the aptitude to growth new nephrons can be triggered in a pathological context. This interesting regenerative property of the elasmobranch kidney relies on the maintenance of the nephron progenitor pool beyond hatching.
We are interested in understanding the physiological and molecular mechanism associated to the maintenance of the elasmobranch nephron progenitors at the post-embryonic stage.
Our model is the small-spotted catshark (Scyliorhinus canicula), an abundant shark of the Northeast Atlantic. It is a small and oviparous species (see a catshark embryo attached to the yolk in Picture 1). The Station Biologique de Roscoff is hosting adult females collected in the field after the mating season. Females are laying eggs throughout the year giving us access to all embryonic stages and juveniles (Lund-Ricard Y and Boutet A. 2021).
Our aim is to characterize nephron progenitor cells both at the embryonic and post-embryonic stage. The progenitors have been histologically identified in several elasmobranch species as mesenchymal cells but no data exist concerning their molecular signatures. Preliminary results indicated that the catshark nephron progenitor cells (NPCs) express transcription factors observed in the mouse and teleost NPCs (see Picture 2). As many vertebrate stem cells have been described to cycle slowly, we are also analysing the cell cycle rhythm of the catshark NPCs using BrdU pulse chase experiment. Stem cells have another interesting property; they are able to maintain a slow global translation rate (see Tahmasebi et al. 2019 for a review concerning Embryonic Stem Cells (ESC), inducible Pluripotent Stem Cells (iPSC), Hematopoietic Stem Cells (HSC), Neural Stem Cells (NSC), satellite cells of the muscle fibre). We are currently exploring the global translation rate of the NPCs in vivo and compare it to their differentiated epithelial counterpart. Several targets of the mTOR pathway, an important regulator of translation initiation (Lund-Ricard Y et al. 2020), are also analysed.
Knowing that individuals with low nephron endowment are at high risk for developing kidney diseases, it is crucial to explore how to extend the process of nephrogenesis in human. The catshark model constitutes a unique model to decipher the mechanism of nephron progenitor maintenance at the post-embryonic stage.
References
- Elger M, Hentschel H, Litteral J, Wellner M, Kirsch T, Luft FC, Haller H. Nephrogenesis is induced by partial nephrectomy in the elasmobranch Leucoraja erinacea. J Am Soc Nephrol. 2003
- Hentschel H. Developing nephrons in adolescent dogfish, Scyliorhinus caniculus (L.), with reference to ultrastructure of early stages, histogenesis of the renal countercurrent system, and nephron segmentation in marine elasmobranchs. Am J Anat. 1991
- Lund-Ricard Y, Cormier P, Morales J, and Boutet A. mTOR Signaling at the Crossroad between Metazoan Regeneration and Human Diseases. Int J Mol Sci. 2020
- Lund-Ricard Y and Boutet A. Current trends in Chondrichthyes experimental biology (2021) In: Boutet, A. & B. Schierwater, eds. Handbook of Established and Emerging Marine Model Organisms in Experimental Biology, CRC Press.
- Tahmasebi S, Amiri M, Sonenberg N. Translational Control in Stem Cells. Front Genet. 2019
We are interested in understanding the physiological and molecular mechanism associated to the maintenance of the elasmobranch nephron progenitors at the post-embryonic stage.
Our model is the small-spotted catshark (Scyliorhinus canicula), an abundant shark of the Northeast Atlantic. It is a small and oviparous species (see a catshark embryo attached to the yolk in Picture 1). The Station Biologique de Roscoff is hosting adult females collected in the field after the mating season. Females are laying eggs throughout the year giving us access to all embryonic stages and juveniles (Lund-Ricard Y and Boutet A. 2021).
Our aim is to characterize nephron progenitor cells both at the embryonic and post-embryonic stage. The progenitors have been histologically identified in several elasmobranch species as mesenchymal cells but no data exist concerning their molecular signatures. Preliminary results indicated that the catshark nephron progenitor cells (NPCs) express transcription factors observed in the mouse and teleost NPCs (see Picture 2). As many vertebrate stem cells have been described to cycle slowly, we are also analysing the cell cycle rhythm of the catshark NPCs using BrdU pulse chase experiment. Stem cells have another interesting property; they are able to maintain a slow global translation rate (see Tahmasebi et al. 2019 for a review concerning Embryonic Stem Cells (ESC), inducible Pluripotent Stem Cells (iPSC), Hematopoietic Stem Cells (HSC), Neural Stem Cells (NSC), satellite cells of the muscle fibre). We are currently exploring the global translation rate of the NPCs in vivo and compare it to their differentiated epithelial counterpart. Several targets of the mTOR pathway, an important regulator of translation initiation (Lund-Ricard Y et al. 2020), are also analysed.
Knowing that individuals with low nephron endowment are at high risk for developing kidney diseases, it is crucial to explore how to extend the process of nephrogenesis in human. The catshark model constitutes a unique model to decipher the mechanism of nephron progenitor maintenance at the post-embryonic stage.
References
- Elger M, Hentschel H, Litteral J, Wellner M, Kirsch T, Luft FC, Haller H. Nephrogenesis is induced by partial nephrectomy in the elasmobranch Leucoraja erinacea. J Am Soc Nephrol. 2003
- Hentschel H. Developing nephrons in adolescent dogfish, Scyliorhinus caniculus (L.), with reference to ultrastructure of early stages, histogenesis of the renal countercurrent system, and nephron segmentation in marine elasmobranchs. Am J Anat. 1991
- Lund-Ricard Y, Cormier P, Morales J, and Boutet A. mTOR Signaling at the Crossroad between Metazoan Regeneration and Human Diseases. Int J Mol Sci. 2020
- Lund-Ricard Y and Boutet A. Current trends in Chondrichthyes experimental biology (2021) In: Boutet, A. & B. Schierwater, eds. Handbook of Established and Emerging Marine Model Organisms in Experimental Biology, CRC Press.
- Tahmasebi S, Amiri M, Sonenberg N. Translational Control in Stem Cells. Front Genet. 2019
