Temporally and spatially regulated collagen XVIII isoforms are involved in ureteric tree development via the TSP1-like domain

Highlights

• Collagen XVIII isoforms have different temporal and spatial expression patterns during renal development.

• The lack of collagen XVIII or its specific isoforms lead to decreased ureteric tree branching and renal hypoplasia, where the domains of the short isoform seem to be most crucial.

• The N-terminal domains of collagen XVIII, and especially its Thrombospondin-1-like domain promote ureteric tree branching and can rescue the branching defect observed in the collagen XVIII-deficient mice.

• The branching promoting effect of the N-terminal domains of collagen XVIII are mediated through integrin α3β1.

Abstract

Collagen XVIII (ColXVIII) is a component of the extracellular matrix implicated in embryogenesis and control of tissue homoeostasis. We now provide evidence that ColXVIII has a specific role in renal branching morphogenesis as observed in analyses of total and isoform-specific knockout embryos and mice. The expression of the short and the two longer isoforms differ temporally and spatially during renal development. The lack of ColXVIII or its specific isoforms lead to congenital defects in the 3D patterning of the ureteric tree where the short isoform plays a prominent role. Moreover, the ex vivo data suggests that ColXVIII is involved in the kidney epithelial tree patterning via its N-terminal domains, and especially the Thrombospondin-1-like domain common to all isoforms. This morphogenetic function likely involves integrins expressed in the ureteric epithelium. Altogether, the results point to an important role for ColXVIII in the matrix-integrin-mediated functions regulating renal development.