TFAP2A orchestrates gene regulatory networks and tubular architecture in kidney outer medullary collecting ducts.

Mutations of the transcription factor TFAP2A are associated with congenital anomalies of the kidney and urinary tract in humans. In mice, deficiency of its ortholog Tfap2a in collecting duct cells causes widened epithelial tubules in the outer medulla of the adult kidney, but the molecular mechanisms of this phenotype are unknown. In this study, we identified gene regulatory networks controlled by Tfap2a in mouse kidney collecting ducts by combining gene knockout and transcriptomics. Integrated analyses of single-nucleus and bulk RNA-sequencing data from kidneys of adult Tfap2a knockout and control mice indicated deregulated expression of genes associated with cell adhesion and Wnt signaling pathways. Validation studies revealed that Tfap2a controls Wnt9b and Alcam, known regulators of kidney tubule morphogenesis. Our data provide novel insights into kidney epithelial gene regulatory networks controlled by Tfap2a and its potential functional role in congenital renal disease. Mouse kidneys (single nucleus preparation) of 12-week-old male Hoxb7Cre+;Tfap2afl/fl (n=2) and control mice (n=2)