ウィルフカン ニ イゾン シタ ミュラーカン ノ シンチョウ セイギョ キコウ ノ ケントウ

熊本大

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

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

Sall4 is not expressed in the Wolffian duct or nephrogenic mesenchyme at E9.5.

<p>(A, B) Bright-field and fluorescence views of <i>Hoxb7GFP</i> and control mice at E9.5. The dotted lines indicate the planes used for the caudal and rostral sections in the following panels. (C, D) Green fluorescent protein staining of caudal and rostral sections from a <i>Hoxb7GFP</i> mouse. (E, F) Sall4 staining of the neighboring sections. (G, H) Sall1 staining of the neighboring sections. Arrowhead: Wolffian duct; arrow: nephrogenic mesenchyme; hg: hindgut; lpm: lateral plate mesoderm; nt: neural tube; pm: paraxial mesoderm. Scale bars: 50 µm.</p

Sall4 is expressed in the caudal Wolffian duct at E10.5.

<p>(A, B) Bright-field and fluorescence views of <i>Hoxb7GFP</i> and control mice at E10.5. The dotted lines indicate the planes used for the caudal and rostral sections. (C, D) Bright-field and fluorescence views of the nephric region of a <i>Hoxb7GFP</i> mouse. (E, F) Green fluorescent protein staining of caudal and rostral sections from a <i>Hoxb7GFP</i> mouse. The right side of panel F is the rostral side. (G, H) Sall4 staining of the neighboring sections. (I, J) Sall1 staining of the neighboring sections. White arrowhead: caudal end of the Wolffian duct; black arrowhead: middle part of the Wolffian duct; red arrowhead: rostral part of the Wolffian duct; white double asterisk: tissues surrounding kidney primordia and hindgut; black asterisk: mesonephric tubule; red asterisk: rostral mesonephric tubule; hg: hindgut; mm: metanephric mesenchyme. Scale bars: 50 µm.</p

<i>Sall4</i> is deleted in the ureteric bud and Wolffian duct in <i>Hoxb7Cre; Sall4</i>^{<i>flox/flox</i>} mice.

<p>(A, B) Hematoxylin and eosin staining of control and <i>Sall4</i> mutant kidneys at E11.5. (C, D) Sall4 staining of the neighboring sections. (E, F) Sall1 staining of the neighboring sections. White arrowhead: caudal end of the Wolffian duct; white double asterisk: tissues surrounding kidney primordia and hindgut; hg: hindgut; mm: metanephric mesenchyme; ub: ureteric bud. Scale bars: 50 µm.</p

Outcomes in Newly Diagnosed Atrial Fibrillation and History of Acute Coronary Syndromes: Insights from GARFIELD-AF

BACKGROUND: Many patients with atrial fibrillation have concomitant coronary artery disease with or without acute coronary syndromes and are in need of additional antithrombotic therapy. There are few data on the long-term clinical outcome of atrial fibrillation patients with a history of acute coronary syndrome. This is a 2-year study of atrial fibrillation patients with or without a history of acute coronary syndromes