The core SWI/SNF catalytic subunit Brg1 regulates nephron progenitor cell proliferation and differentiation

Jeannine M. Basta, Ajeet P. Singh, Lynn Robbins, Lisa Stout, Michelle Pherson, Michael Rauchman

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Chromatin-remodeling complexes play critical roles in establishing gene expression patterns in response to developmental signals. How these epigenetic regulators determine the fate of progenitor cells during development of specific organs is not well understood. We found that genetic deletion of Brg1 (Smarca4), the core enzymatic protein in SWI/SNF, in nephron progenitor cells leads to severe renal hypoplasia. Nephron progenitor cells were depleted in Six2-Cre, Brg1flx/flx mice due to reduced cell proliferation. This defect in self-renewal, together with impaired differentiation resulted in a profound nephron deficit in Brg1 mutant kidneys. Sall1, a transcription factor that is required for expansion and maintenance of nephron progenitors, associates with SWI/SNF. Brg1 and Sall1 bind promoters of many progenitor cell genes and regulate expression of key targets that promote their proliferation.

Original languageEnglish
Pages (from-to)176-187
Number of pages12
JournalDevelopmental Biology
Volume464
Issue number2
DOIs
StatePublished - Aug 15 2020

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