Haploinsufficiency for the Six2 gene increases nephron progenitor proliferation promoting branching and nephron number.

ABSTRACT: The regulation of final nephron number in the kidney is poorly understood. Cessation of nephron formation occurs when the self-renewing nephron progenitor population commits to differentiation. Transcription factors within this progenitor population, such as SIX2, are assumed to control expression of genes promoting self-renewal such that homozygous Six2 deletion results in premature commitment and an early halt to kidney development. In contrast, Six2 heterozygotes were assumed to be unaffected. Using quantitative morphometry, we found a paradoxical 18% increase in ureteric branching and final nephron number in Six2 heterozygotes, despite evidence for reduced levels of SIX2 protein and transcript. This was accompanied by a clear shift in nephron progenitor identity with a distinct subset

SUBMITTER: Combes AN 

PROVIDER: S-EPMC6361385 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature