Lim1 is required for nephric duct extension and ureteric bud morphogenesis

Abstract

The nephric duct plays a central role in orchestrating the development of the mammalian urogenital system. Lim 1 is a homeobox gene required for head and urogenital development in the mouse but most Lim 1-deficient embryos die by embryonic day 10. To determine the role of Lim 1 in the development of the nephric duct, we conditionally removed Lim 1 in the nephric epithelium just after the nephric duct begins to form using a floxed allele of Lim 1 and Pax2-cre transgenic mice. We report that Lim 1 conditional knockout mice have renal hypoplasia and hydronephrosis. Developmental studies revealed that the caudal portion of the nephric duct did not reach the urogenital sinus at embryonic day 10.5, formation of the ureteric bud was delayed, the ureteric bud was smaller and branching of the ureteric bud reduced. We also found that the nephric duct was generally not maintained and extension of the Müllerian duct inhibited. Molecular analysis indicated that Pax2 was expressed normally but the expression of Wnt9b and E-cadherin in the nephric duct was markedly altered. These results suggest that Lim 1 influences nephric duct extension and ureteric bud outgrowth by regulating and or maintaining the differentiation of the nephric epithelium.

Heat Shock 70-kDa Protein 5 (Hspa5) Is Essential for Pronephros Formation by Mediating Retinoic Acid Signaling

“…lhx1 encodes one of the earliest transcription factors that is expressed in the pronephric anlagen and is directly regulated by RA signaling. During kidney organogenesis, Lhx1 is essential for tubule morphogenesis, duct extension, and glomerulus development (20,61,62). In Xenopus, a dominant-negative Lhx1 inhibited differentiation of pronephros derived from animal caps treated with activin and atRA (22).…”

p53 Regulates Metanephric Development

“…The latter effect may explain the extrarenal nodules and pitting of the kidney surface as a result of patterning defects observed in UB p53DN mice. Several current models of supernumerary budding cite aberrant expression or signaling along the GDNF-cRet-Spry1 pathway as the primary defect leading to ectopic budding 13,14,17,40 ; however, there are other genetic models, such as conditional ␤-catenin WD and Lim1 mice, 41,42 that do not. In our model of ectopic budding, we did not observe an expanded GDNF domain or changes in c-Ret or Sprouty1 expression.…”

“…Differential cell adhesion has been postulated as a cause of ectopic bud formation. 41,42 p53 is a known regulator of adhesion molecule expression such as E-cadherin, 43 as well as of adhesion-associated molecules such as Perp. 44,45 Comparing adhesion and migration differences in cells from p53-mutant ducts, although challenging, will offer much insight into mechanisms of UB outgrowth.…”

Congenital Obstructive Nephropathy: Clinical Perspectives and Animal Models

“…Developmental urinary tract anomalies including hydronephrosis also arise from knockout of the uroplakin II or III genes and conditional knockout of homeobox gene Lim1 in the nephric duct epithelium (Hu et al, 2000;Kong et al, 2004;Pedersen et al, 2005). However, VUR is also a prominent feature in these CAKUT models, and it is not clear whether there is a true or a functional obstruction, nor what the relative contributions of reflux and obstruction to the renal phenotype are.…”