The Expression of Transcription Factors in Fetal Lamb Kidney.

Yuri Nishiya,Kei Ohyama,Kosuke Kudo,Kohei Kawaguchi,Hiroaki Kitagawa,Kevin C Pringle,Juma Obayashi,Takuya Kawaguchi,Kunihide Tanaka,Junki Koike,Shigeyuki Furuta,Hideki Nagae,Yasuji Seki

doi:10.3390/jdb9020022

Abstract

(1) Background: Renal development involves frequent expression and loss of transcription factors, resulting in the activation of genes. Wilms’ tumor 1 (WT1), hepatocyte nuclear factor-1-beta (HNF1β), and paired box genes 2 and 8 (Pax2 and Pax8) play an important role in renal development. With this in vivo study, we examined the period and location of expression of these factors in renal development. (2) Methods: Fetal lamb kidneys (50 days from gestation to term) and adult ewe kidneys were evaluated by hematoxylin and eosin staining. Serial sections were subjected to immunohistochemistry for WT1, HNF1β, Pax2, and Pax8. (3) Results: Pax2, Pax8, and HNF1β expression was observed in the ureteric bud and collecting duct epithelial cells. We observed expression of WT1 alone in metanephric mesenchymal cells, glomerular epithelial cells, and interstitial cells in the medullary rays and Pax8 and HNF1β expression in tubular epithelial cells. WT1 was highly expressed in cells more proximal to the medulla in renal vesicles and in C- and S-shaped bodies. Pax2 was expressed in the middle and peripheral regions, and HNF1β in cells in the region in the middle of these. (4) Conclusions: WT1 is involved in nephron development. Pax2, Pax8, and HNF1β are involved in nephron maturation and the formation of peripheral collecting ducts from the Wolffian duct.

Highlights

The development of the mammalian kidney starts from interactions between the Wolffian duct and the metanephric mesenchyme (MM)
It was reported that: (i) SIX2, SALL1, Wilms’ tumor 1 (WT1), and paired box gene 2 (Pax2)-positive nephron progenitor cells (NPCs) are induced by human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs) through the primitive streak and posterior intermediate mesoderm; and (ii) the NPCs result in pretubular aggregates and paired box gene 8 (Pax8), LHX1, and LAM-positive renal vesicles with the expression of hepatocyte nuclear factor-1-beta (HNF1β) and BRN1, subsequently inducing the podocytes, proximal tubule, Henle’s loop, and distal tubule [3]
In this in vivo study, we examined fetal lamb kidneys using immunohistochemistry to determine the location and timing of the expression of transcription factors WT1, HNF1β, Pax2, and Pax8, which have been reported to be involved in renal development

Summary

Introduction

The development of the mammalian kidney starts from interactions between the Wolffian duct and the metanephric mesenchyme (MM). As the branching of the UB nears its completion, the terminal ends of the UB branches fuse with the distal ends of the developing nephrons and the UB differentiates into the collecting ducts, which drain into the renal pelvis This process occurs intermittently during the fetal stage, leading to the formation of a mature kidney [1]. It was reported that: (i) SIX2, SALL1, WT1, and paired box gene 2 (Pax2)-positive nephron progenitor cells (NPCs) are induced by hESCs and hiPSCs through the primitive streak and posterior intermediate mesoderm; and (ii) the NPCs result in pretubular aggregates and paired box gene 8 (Pax8), LHX1, and LAM-positive renal vesicles with the expression of hepatocyte nuclear factor-1-beta (HNF1β) and BRN1, subsequently inducing the podocytes, proximal tubule, Henle’s loop, and distal tubule [3]

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Discussion

Conclusion