Sonic Hedgehog Mediator Gli2 Regulates Bladder Mesenchymal Patterning

Wei, Cheng; Yeung, Chung‐Kwong; Ng, Yuen-Keng; Zhang, Jianrong; Hui, Chi‐chung; Kim, Peter C.W.

doi:10.1016/j.juro.2008.06.003

Cited by 37 publications

(48 citation statements)

References 27 publications

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“…The muscle forms via interactions between the urothelium and surrounding mesenchyme (Cunha, 1999). Recent studies of environmental factors, epithelial-tomesenchymal interactions and signalling pathways required for bladder smooth muscle formation have advanced our understanding of this developmental process (Cao et al, 2008Cheng et al, 2008;DeSouza et al, 2013;Haraguchi et al, 2007;Liu et al, 2010;Shiroyanagi et al, 2007;Tasian et al, 2010). We have updated the bladder ontology to incorporate these findings (Fig.…”

Section: Regional and Cellular Updates To The Bladder And Urethra Ontmentioning

confidence: 99%

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An illustrated anatomical ontology of the developing mouse lower urogenital tract

et al. 2015

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Malformation of the urogenital tract represents a considerable paediatric burden, with many defects affecting the lower urinary tract (LUT), genital tubercle and associated structures. Understanding the molecular basis of such defects frequently draws on murine models. However, human anatomical terms do not always superimpose on the mouse, and the lack of accurate and standardised nomenclature is hampering the utility of such animal models. We previously developed an anatomical ontology for the murine urogenital system. Here, we present a comprehensive update of this ontology pertaining to mouse LUT, genital tubercle and associated reproductive structures (E10.5 to adult). Ontology changes were based on recently published insights into the cellular and gross anatomy of these structures, and on new analyses of epithelial cell types present in the pelvic urethra and regions of the bladder. Ontology changes include new structures, tissue layers and cell types within the LUT, external genitalia and lower reproductive structures. Representative illustrations, detailed text descriptions and molecular markers that selectively label muscle, nerves/ganglia and epithelia of the lower urogenital system are also presented. The revised ontology will be an important tool for researchers studying urogenital development/malformation in mouse models and will improve our capacity to appropriately interpret these with respect to the human situation.

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Section: Regional and Cellular Updates To The Bladder And Urethra Ontmentioning

confidence: 99%

“…Actin alpha-smooth muscle (Acta2) is utilised as a marker of early differentiation (Fig. 7G,H,K) and smooth muscle heavy chain myosin (Myh11) marks more advanced differentiation (Cheng et al, 2008;DeSouza et al, 2013;Liu et al, 2010;Shiroyanagi et al, 2007).…”

Section: Regional and Cellular Updates To The Bladder And Urethra Ontmentioning

confidence: 99%

An illustrated anatomical ontology of the developing mouse lower urogenital tract

et al. 2015

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“…-/-double mutants, which suggests that the limited degree of cloacal septation in Shh -/-mice does not occur when the hedgehog pathway is completely inactivated (Cheng et al, 2008). Recent examination of the zebrafish anogenital system, which undergoes septation, also found a requirement for Hedgehog signaling during cloacal development, with, the most severe anorectal defects occurring in smu (smoothened) mutants or in embryos treated with cyclopamine (Parkin et al, 2009).…”

Section: Multiphasic Role Of Shh In Anogenital Developmentmentioning

confidence: 99%

“…The range of phenotypes observed when Shh was inactivated between E9.5 and 11.5 resembled those reported for Gli2/3 double null mutants ). Gli2 -/-and Gli3 -/-mutants display normal genital tubercle outgrowth, indicating redundancy in the genital tubercle, but Gli2 is necessary for extension of the hindgut to the cloacal membrane (Cheng et al, 2008;Kimmel et al, 2000;Mo et al, 2001). Removal of one or both copies of Gli3 in a Gli2 -/-background does not increase the severity of the septation defect.…”

Section: Abnormal Morphogenesis Of Hindgut Epithelium Is An Indirect mentioning

confidence: 99%

“…Work by a number of labs has shown that Shh is required for outgrowth and patterning of the genital tubercle and for division of the cloaca into separate urogenital and anorectal sinuses. Shh -/-mice have complete agenesis of the external genitalia and persistence of the cloaca (Cheng et al, 2008;Haraguchi et al, 2001;Kim et al, 2001;Kimmel et al, 2000;Perriton et al, 2002). In humans, mutations affecting Hedgehog signaling and its downstream targets have been linked to syndromes involving ARM, such as the VACTERL complex, Pallister-Hall and Townes-Brocks syndromes (Kang et al, 1997;Kohlhase et al, 1998;Mo et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Multiphasic and tissue-specific roles of sonic hedgehog in cloacal septation and external genitalia development

et al. 2009

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Malformations of the external genitalia are among the most common congenital anomalies in humans. The urogenital and anorectal sinuses develop from the embryonic cloaca, and the penis and clitoris develop from the genital tubercle. Within the genital tubercle, the endodermally derived urethral epithelium functions as an organizer and expresses sonic hedgehog (Shh). Shh knockout mice lack external genitalia and have a persistent cloaca. This identified an early requirement for Shh, but precluded analysis of its later role in the genital tubercle. We conducted temporally controlled deletions of Shh and report that Shh is required continuously through the onset of sexual differentiation. Shh function is divisible into two temporal phases; an anogenital phase, during which Shh regulates outgrowth and patterning of the genital tubercle and septation of the cloaca, and a later external genital phase, during which Shh regulates urethral tube closure. Disruption of Shh function during the anogenital phase causes coordinated anorectal and genitourinary malformations, whereas inactivation during the external genital phase causes hypospadias. Shh directs cloacal septation by promoting cell proliferation in adjacent urorectal septum mesenchyme. Additionally, conditional inactivation of smoothened in the genital ectoderm and cloacal/urethral endoderm shows that the ectoderm is a direct target of Shh and is required for urethral tube closure, highlighting a novel role for genital ectoderm in urethragenesis. Identification of the stages during which disruption of Shh results in either isolated or coordinated malformations of anorectal and external genital organs provides a new tool for investigating the etiology of anogenital malformations in humans.

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Urothelial generation and regeneration in development, injury, and cancer

Wang

Ross

Mysorekar

2017

Developmental Dynamics

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Homeostatic maintenance and repair of the urothelium upon injury are required for a functional bladder in both healthy and disease conditions. Understanding the cellular and molecular mechanisms underlying the urothelial regenerative response is key to designing strategies for tissue repair and ultimately treatments for urologic diseases including urinary tract infections, voiding dysfunction, painful bladder syndrome and bladder cancer. In this article, we review studies on urothelial ontogeny during development and regeneration following various injury modalities. Signaling pathways involved in urothelial regeneration and in urothelial carcinogenesis are also discussed.

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Sonic Hedgehog Mediator Gli2 Regulates Bladder Mesenchymal Patterning

Abstract: Our data suggests that the Shh transcriptional factor Gli2 regulates radial patterning of the bladder mesenchyma.

Cited by 37 publications

References 27 publications

An illustrated anatomical ontology of the developing mouse lower urogenital tract

An illustrated anatomical ontology of the developing mouse lower urogenital tract

Multiphasic and tissue-specific roles of sonic hedgehog in cloacal septation and external genitalia development

Urothelial generation and regeneration in development, injury, and cancer

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