Transient versican expression is required for β1-Integrin accumulation during podocyte layer morphogenesis in amphibian developing kidney

The functional organization of the vertebrate nephron is remarkably conserved. However, the morphogenetic processes underlying nephrogenesis can vary significantly across species and various kinds of kidneys. The Xenopus larval kidney, the pronephros, is a non-integrated nephron where plasma filtrates are first release into a coelomic compartment, the nephrocoel, before being released into the tubular compartment through ciliated funnels called nephrostome. Mechanisms of pronephros morphogenesis, especially the potential role of the extracellular matrix (ECM) remain poorly understood. This study investigates the role of the ECM component versican (vcan) in the development of the pronephric kidney in X. laevis, paying a special attention to non-integrated nephron features, the glomus, nephrocoel and nephrostomes. Vcan is dynamically expressed in the ECM surrounding the developing tubule and the podocyte layer of the glomus, with a transient presence in the differentiating podocyte-region prior to the formation of the concave podocyte pocket accumulating β1-integrin. Morpholino depletion of vcan causes a fusion of the proximal tubule branches without affecting the nephrostomes. Tubules become dilated and lose their proximal circumvolutions. More strikingly, vcan depletion results in a severe disruption of glomus morphogenesis, the podocyte layer failing to form its characteristic C-shaped structure. Despite normal expression of the differentiation markers nphs2 in podocytes, β1-integrin fails to accumulate in the podocyte layer in vcan-depleted embryos. Interestingly, other ECM components, including fibrillin, laminin, and fibronectin, remain correctly localized, suggesting that the defect is not due to a general ECM disorganization. These findings reveal that transient vcan expression is critical for podocytes layer morphogenesis, likely by enabling β1-integrin accumulation and subsequent cell-ECM interactions necessary for structural assembly. The study highlights a specific and temporally regulated role of vcan in glomus morphogenesis, expanding our understanding of ECM dynamics in kidney development.