Unraveling the origin of the vertebrate kidney: Emergence from a somitic compartment
Somite compartmentalization and kidney development are considered as two distinct developmental processes. It is widely acknowledged that in amniotes as well as in frogs and bony fish, the pronephros and therefore the adult kidney develop from the intermediate mesoderm. Our study sheds light on the evolution of pronephros formation in vertebrates, revealing its ancient origin from a specific, segmented, somitic subterritory, the nephrotome, which buds off during early development to create the nephric duct. In nonvertebrate chordates, mesoderm markers are expressed in common progenitor cells of dermomyotome and nephrotome, whereas in cyclostomes and elasmobranchs, they segregate into distinctive domains within the somite. Two main discoveries are thus described here: (i) The intermediate mesoderm originated developmentally and evolutionarily from a specific domain within somitic tissues, and (ii) the pronephric progenitor cell domain is redefined as the fifth somitic compartment, the nephrotome, alongside the dermatome, myotome, syndetome, and sclerotome. Our results support the hypothesis that this fifth somitic domain, the nephrotome, is the evolutionary predecessor of the intermediate mesoderm, giving rise to the pronephros and hence to the adult kidney.
Authors
- João E. Carvalho (ORCID: https://orcid.org/0000-0002-7770-4351)
- Ronit Yelin
- Michael Schubert (ORCID: https://orcid.org/0000-0002-2341-712X)
- Matteo Bozzo (ORCID: https://orcid.org/0000-0002-7452-3758)
- Eva Leman
- Ketty Hakim‐Mishnaevski (ORCID: https://orcid.org/0000-0002-6227-3886)
- Sylvie Mazan (ORCID: https://orcid.org/0000-0003-4657-8097)
- Pascal Schmidt (ORCID: https://orcid.org/0009-0009-8628-684X)
- Haneen Kayyal (ORCID: https://orcid.org/0000-0003-4429-3514)
- Boris Shklyar (ORCID: https://orcid.org/0000-0003-2018-636X)
- Ram Reshef
- Lagadec Ronan (ORCID: https://orcid.org/0009-0008-9418-6040)
- Nadeen Dai
Institutions
- Centre National de la Recherche Scientifique (FR)
- Technion – Israel Institute of Technology (IL)
- Sorbonne Université (FR)
- Rappaport Family Institute for Research in the Medical Sciences (IL)
- Biologie Intégrative des Organismes Marins (FR)
- Laboratoire de Biologie du Développement de Villefranche-sur-Mer (FR)
- Institut de la Mer de Villefranche (FR)
- University of Genoa (IT)
- University of Haifa (IL)
Publication Details
- Journal
- Science Advances
- Published
- 2026-06-26
- DOI
- https://doi.org/10.1126/sciadv.adr2618
- Primary Topic
- Renal and related cancers
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Horizon Therapeutics
- Agence Nationale de la Recherche
- Israel Science Foundation
- Centre National de la Recherche Scientifique
- Conseil National de la Recherche Scientifique
- Association Neurofibromatoses et Recklinghause
- Horizon 2020 Framework Programme