Transient versican expression is required for β1-integrin accumulation during podocyte layer morphogenesis in...

The functional organization of the vertebrate nephron is remarkably conserved, yet the morphogenetic processes underlying nephrogenesis vary across species and kidney types. The Xenopus larval kidney, the pronephros, is a non-integrated nephron where plasma filtrates are first released into a coelomic compartment, the nephrocoel, before entering the tubular compartment through ciliated nephrostomes. Mechanisms of pronephros morphogenesis, especially the role of the extracellular matrix (ECM), remain poorly understood. This study investigates the function of the ECM component versican (vcan) in the development of the pronephric kidney in X. laevis, focusing on 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 transient presence in the differentiating podocyte region prior to the formation of the concave podocyte pocket that accumulates β1-integrin. Morpholino-mediated vcan depletion leads to fusion of proximal tubule branches, tubular dilation, and loss of proximal convolutions, without affecting nephrostomes. Glomus morphogenesis is severely disrupted, the podocyte layer fails to form its characteristic C-shaped structure, and β1-integrin fails to accumulate, although the podocyte differentiation marker nphs2 remains expressed. Other ECM components, including fibrillin, laminin, and fibronectin, remain correctly localized, indicating that the phenotype is not due to general ECM disorganization. Together, these findings identify a specific and temporally regulated role for vcan in glomus morphogenesis, likely by enabling β1-integrin accumulation and promoting cell-ECM interactions essential for proper podocyte layer assembly, thereby refining our understanding of ECM dynamics in kidney development.