Elsevier

Developmental Biology

Volume 464, Issue 2, 15 August 2020, Pages 176-187
Developmental Biology

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

https://doi.org/10.1016/j.ydbio.2020.05.008Get rights and content
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Highlights

  • Brg1, the core enzymatic subunit of SWI/SNF, is required for growth of the developing kidney.

  • Sall1 cooperates with Brg1 to regulate expansion of nephron progenitor cells.

  • Bmp7, Fgf9 and Myc are direct transcriptional targets of Sall1 and Brg1.

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.

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These authors contributed equally to this work.