FOXD1 is required for 3D patterning of the kidney interstitial matrix

BackgroundThe interstitial extracellular matrix (ECM) is comprised of proteins and glycosaminoglycans and provides structural and biochemical information during development. Our previous work revealed the presence of transient ECM-based structures in the interstitial matrix of developing kidneys. Stromal cells are the main contributors to interstitial ECM synthesis, and the transcription factor Forkhead Box D1 (Foxd1) is critical for stromal cell function. To investigate the role of Foxd1 in interstitial ECM patterning, we combined 3D imaging and proteomics to explore how the matrix changes in the murine developing kidney when Foxd1 is knocked out. ResultsWe found that COL26A1, FBN2, EMILIN1, and TNC, interstitial ECM proteins that are transiently upregulated during development, had a similar distribution perinatally but then diverged in patterning in the adult. Abnormally clustered cortical vertical fibers and fused glomeruli were observed when Foxd1 was knocked out. The changes in the interstitial ECM of Foxd1 knockout kidneys corresponded to disrupted Foxd1(+) cell patterning but did not precede branching dysmorphogenesis. ConclusionsThe transient ECM networks affected by Foxd1 knockout may provide support for later-stage nephrogenic structures.

Automated summary

The study found that when the Foxd1 gene was knocked out in the developing kidney of mice, there were differences in the patterning of the extracellular matrix (ECM) proteins, including COL26A1, FBN2, EMILIN1, and TNC. These changes correlated with disrupted patterning of Foxd1(+) cells, but did not occur before branching dysmorphogenesis.