Transcription Factors YAP/TAZ and SRF Cooperate to Specify Renal Myofibroblasts in the Developing Mouse Kidney

Keri A. Drake, Christopher Chaney, Mohita Patel, Amrita Das, Julia Bittencourt, Martin Cohn, Thomas J Carroll

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background The embryonic renal stroma consists of multiple molecularly distinct cell subpopulations, the functional significance of which is largely unknown. Previous work has demonstrated that the transcription factors YAP and TAZ play roles in the development and morphogenesis of the nephrons, collecting ducts, and nephron progenitor cells. Methods In embryonic mouse kidneys, we identified a subpopulation of stromal cells with enriched activity in YAP and TAZ. To evaluate the function of these cell types, we genetically ablated both Yap and Taz from the stromal progenitor population and examined how gene activity and development of YAP/TAZ mutant kidneys are affected over a developmental time course. Results We found that YAP and TAZ are active in a subset of renal interstitium and that stromal-specific coablation of YAP/TAZ disrupts cortical fibroblast, pericyte, and myofibroblast development, with secondary effects on peritubular capillary differentiation. We also demonstrated that the transcription factor SRF cooperates with YAP/TAZ to drive expression of at least a subset of renal myofibroblast target genes and to specify myofibroblasts, but not cortical fibroblasts or pericytes. Conclusions These findings reveal a critical role for YAP/TAZ in specific embryonic stromal cells and suggest that interaction with cofactors, such as SRF, influence the expression of cell type–specific target genes, thus driving stromal heterogeneity. Further, this work reveals functional roles for renal stroma heterogeneity in creating unique microenvironments that influence the differentiation and maintenance of the renal parenchyma.

Original languageEnglish (US)
Pages (from-to)1694-1707
Number of pages14
JournalJournal of the American Society of Nephrology
Volume33
Issue number9
DOIs
StatePublished - Sep 2022

ASJC Scopus subject areas

  • Nephrology

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