Urothelial sonic hedgehog signaling plays an important role in bladder smooth muscle formation

Shiroyanagi, Yoshiyuki; Liu, Benchun; Cao, Mei; Agras, Koray; Jiang, Li; Hsieh, Michael H.; Willingham, Emily; Baskin, Laurence S.

doi:10.1111/j.1432-0436.2007.00187.x

Cited by 56 publications

(72 citation statements)

References 35 publications

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“…To identify potential candidates, we focused on Shh because its activity is crucial for proliferation of the surrounding mesenchyme and differentiation of smooth muscle cells (DeSouza et al, 2013;Shin et al, 2011;Shiroyanagi et al, 2007). Shh and its receptors Ptch1 and Ptch2 were significantly reduced in Eed cKO Shh mutant bladders compared with expression in bladders of littermate controls ( Fig.…”

Section: Prc2 Regulates Shh Expression In Urothelial Progenitorsmentioning

confidence: 99%

Stage- and subunit-specific functions of polycomb repressive complex 2 in bladder urothelial formation and regeneration

et al. 2017

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Urothelium is the protective lining of the urinary tract. The mechanisms underlying urothelial formation and maintenance are largely unknown. Here, we report the stage-specific roles of PRC2 epigenetic regulators in embryonic and adult urothelial progenitors. Without Eed, the obligatory subunit of PRC2, embryonic urothelial progenitors demonstrate reduced proliferation with concomitant dysregulation of genes including Cdkn2a ( p16), Cdkn2b ( p15) and Shh. These mutants display premature differentiation of keratin 5-positive (Krt5 + ) basal cells and ectopic expression of squamouslike differentiation markers. Deletion of Ezh2, the major enzymatic component of PRC2, causes upregulation of Upk3a + superficial cells. Unexpectedly, Eed and Eed/Ezh2 double mutants exhibit delayed superficial cell differentiation. Furthermore, Eed regulates the proliferative and regenerative capacity of adult urothelial progenitors and prevents precocious differentiation. Collectively, these findings uncover the epigenetic mechanism by which PRC2 controls urothelial progenitor cell fate and the timing of differentiation, and further suggest an epigenetic basis of urothelial maintenance and regeneration.

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Section: Prc2 Regulates Shh Expression In Urothelial Progenitorsmentioning

confidence: 99%

Stage- and subunit-specific functions of polycomb repressive complex 2 in bladder urothelial formation and regeneration

et al. 2017

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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%

“…In the primitive bladder, the strongest expression is seen in a thin layer of the mesenchyme immediately underneath the urothelium, resulting in radial patterning of the mesenchyme. This sub-urothelial layer remains devoid of smooth muscle cells throughout development (Cao et al, 2008Shiroyanagi et al, 2007;Fig. 7).…”

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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“…At E13.5, the bladder urothelium induces the surrounding mesenchyme to begin differentiating into the inner lamina propria and outer smooth muscle layers (5). Secretion of sonic hedgehog (Shh) by the bladder urothelium is a major inducer for mesenchymal patterning (5,7,8,20). The E16.5 bladder begins receiving urine from the newly developed metanephric nephrons.…”

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confidence: 99%

Fgfr2 is integral for bladder mesenchyme patterning and function

Walker

Ikeda

Zabbarova

et al. 2015

American Journal of Physiology-Renal Physiology

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BMϪ/Ϫ bladders exhibited higher levels of Cdo and Boc, hedgehog coreceptors that enhance sensitivity to Shh, compared with control bladders. In conclusion, loss of Fgfr2 in the bladder mesenchyme leads to abnormal bladder morphology and decreased compliance and contractility. bladder development; bladder dysfunction; fibroblast growth factor receptor 2 MURINE BLADDER DEVELOPMENT begins at embryonic day (E)10.5, when the cloaca is subdivided into the urogenital sinus ventrally and the anal canal dorsally (5). At E13.5, the bladder urothelium induces the surrounding mesenchyme to begin differentiating into the inner lamina propria and outer smooth muscle layers (5). Secretion of sonic hedgehog (Shh) by the bladder urothelium is a major inducer for mesenchymal patterning (5,7,8,20). The E16.5 bladder begins receiving urine from the newly developed metanephric nephrons.

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Urothelial sonic hedgehog signaling plays an important role in bladder smooth muscle formation

Cited by 56 publications

References 35 publications

Stage- and subunit-specific functions of polycomb repressive complex 2 in bladder urothelial formation and regeneration

Stage- and subunit-specific functions of polycomb repressive complex 2 in bladder urothelial formation and regeneration

An illustrated anatomical ontology of the developing mouse lower urogenital tract

Fgfr2 is integral for bladder mesenchyme patterning and function

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