Sall4 Is Transiently Expressed in the Caudal Wolffian Duct and the Ureteric Bud, but Dispensable for Kidney Development

Daichi Toyoda,Atsuhiro Taguchi,Tomoko Ohmori,Ryuichi Nishinakamura,Masahiko Chiga,Christoph Englert

doi:10.1371/journal.pone.0068508

Abstract

The kidney, the metanephros, is formed by reciprocal interactions between the metanephric mesenchyme and the ureteric bud, the latter of which is derived from the Wolffian duct that elongates in the rostral-to-caudal direction. Sall1 expressed in the metanephric mesenchyme is essential for ureteric bud attraction in kidney development. Sall4, another member of the Sall gene family, is required for maintenance of embryonic stem cells and establishment of induced pluripotent stem cells, and is thus considered to be one of the stemness genes. Sall4 is also a causative gene for Okihiro syndrome and is essential for the formation of many organs in both humans and mice. However, its expression and role in kidney development remain unknown, despite the essential role of Sall1 in the metanephric mesenchyme. Here, we report that mouse Sall4 is expressed transiently in the Wolffian duct-derived lineage, and is nearly complementary to Sall1 expression. While Sall4 expression is excluded from the Wolffian duct at embryonic (E) day 9.5, Sall4 is expressed in the Wolffian duct weakly in the mesonephric region at E10.5 and more abundantly in the caudal metanephric region where ureteric budding occurs. Sall4 expression is highest at E11.5 in the Wolffian duct and ureteric bud, but disappears by E13.5. We further demonstrate that Sall4 deletion in the Wolffian duct and ureteric bud does not cause any apparent kidney phenotypes. Therefore, Sall4 is expressed transiently in the caudal Wolffian duct and the ureteric bud, but is dispensable for kidney development in mice.

Highlights

The mammalian kidney, the metanephros, is formed by reciprocally inductive interactions between two precursor tissues, the metanephric mesenchyme and the ureteric bud [1]
green fluorescent protein (GFP)-positive Wolffian ducts were detected adjacent to the nephrogenic mesenchyme in both the caudal and rostral parts (Figure 1C, D)
Sall4 expression was undetectable in the Wolffian ducts and the nephrogenic mesenchyme, while its expression was detected in other areas, including the hindgut, lateral plate mesoderm, paraxial mesoderm, and neural tubes (Figure 1E, F)

Summary

Introduction

The mammalian kidney, the metanephros, is formed by reciprocally inductive interactions between two precursor tissues, the metanephric mesenchyme and the ureteric bud [1]. The mesenchyme attracts the ureteric bud, while the ureteric bud induces the mesenchyme to differentiate into the epithelia of the glomeruli and renal tubules. The ureteric buds branch and differentiate into collecting ducts and the ureter. The ureteric bud is derived from the Wolffian duct (nephric duct) that elongates in the rostral-to-caudal direction and reaches the caudal end of the embryo at embryonic (E) day 9.5. At E10.5, the Wolffian duct stimulates the nephrogenic mesenchyme to form mesonephric tubules [2]. The caudal end of the Wolffian duct adjacent to the metanephric mesenchyme bulges, from which ureteric budding occurs at E11.0. The ureteric bud elongates and starts to branch

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Results

Conclusion