Lin28 Sustains Early Renal Progenitors and Induces Wilms Tumor

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2014 Apr 16

PMID 24732380

Citations 92

Authors

Achia Urbach

Alena Yermalovich

Jin Zhang

Catherine S Spina

Hao Zhu

Antonio R Perez-Atayde

Rachel Shukrun

Jocelyn Charlton

Neil Sebire

William Mifsud

Benjamin Dekel

Kathy Pritchard-Jones

George Q Daley

Affiliations

Soon will be listed here.

Abstract

Wilms Tumor, the most common pediatric kidney cancer, evolves from the failure of terminal differentiation of the embryonic kidney. Here we show that overexpression of the heterochronic regulator Lin28 during kidney development in mice markedly expands nephrogenic progenitors by blocking their final wave of differentiation, ultimately resulting in a pathology highly reminiscent of Wilms tumor. Using lineage-specific promoters to target Lin28 to specific cell types, we observed Wilms tumor only when Lin28 is aberrantly expressed in multiple derivatives of the intermediate mesoderm, implicating the cell of origin as a multipotential renal progenitor. We show that withdrawal of Lin28 expression reverts tumorigenesis and markedly expands the numbers of glomerulus-like structures and that tumor formation is suppressed by enforced expression of Let-7 microRNA. Finally, we demonstrate overexpression of the LIN28B paralog in a significant percentage of human Wilms tumor. Our data thus implicate the Lin28/Let-7 pathway in kidney development and tumorigenesis.

Citing Articles

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