Abstract
The formation of the proper number of nephrons requires a tightly regulated balance between renal progenitor cell self-renewal and differentiation. The molecular pathways that regulate the transition from renal progenitor to renal vesicle are not well understood. Here, we show that Sall1interacts with the nucleosome remodeling and deacetylase complex (NuRD) to inhibit premature differentiation of nephron progenitor cells. Disruption of Sall1-NuRD in vivo in knock-in mice (ΔSRM) resulted in accelerated differentiation of nephron progenitors and bilateral renal hypoplasia. Transcriptional profiling of mutant kidneys revealed a striking pattern in which genes of the glomerular and proximal tubule lineages were either unchanged or upregulated, and those in the loop of Henle and distal tubule lineages were downregulated. These global changes in gene expression were accompanied by a significant decrease in THP-, NKCC2- and AQP1-positive loop of Henle nephron segments in mutant ΔSRM kidneys. These findings highlight an important function of Sall1-NuRD interaction in the regulation of Six2-positive multipotent renal progenitor cells and formation of the loop of Henle.
Recommended Citation
J. M. Basta et al., "A Sall1-NuRD Interaction Regulates Multipotent Nephron Progenitors And Is Required For Loop Of Henle Formation," Development Cambridge, vol. 144, no. 17, pp. 3080 - 3094, The Company of Biologists, Sep 2017.
The definitive version is available at https://doi.org/10.1242/dev.148692
Department(s)
Biological Sciences
Publication Status
Free Access
Keywords and Phrases
Lgr5; Loop of henle; Nephron progenitor; NuRD; Sall1
International Standard Serial Number (ISSN)
1477-9129; 0950-1991
Document Type
Article - Journal
Document Version
Final Version
File Type
text
Language(s)
English
Rights
© 2025 The Authors, All rights reserved.
Publication Date
01 Sep 2017
PubMed ID
28760814
Comments
National Institute of Diabetes and Digestive and Kidney Diseases, Grant R01DK098563