3‐dimensional morphometric analysis of murine bladder development and dysmorphogenesis

Carpenter, Ashley R.; Paulus, Andrew; Robinson, Melissa; Bates, Carlton M.; Robinson, Michael L.; Kline, David D.; McHugh, Kirk M.

doi:10.1002/dvdy.23744

Cited by 9 publications

(12 citation statements)

References 33 publications

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“…Detrusor smooth muscle differentiation initiates in the bladder dome region and subsequently progresses caudally with the leading edge extending down the right posterior surface of the bladder during murine bladder development [19]. There is also evidence of 2 main interstitial cell populations in the upper and deeper lamina propria in the human bladder dome region, which have distinct ultrastructural and immunohistochemical phenotypes [20].…”

Section: Discussionmentioning

confidence: 99%

A Feasibility Study to Determine Whether Clinical Contrast Enhanced Magnetic Resonance Imaging can Detect Increased Bladder Permeability in Patients with Interstitial Cystitis

Towner

Wisniewski

et al. 2016

Journal of Urology

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Purpose Interstitial cystitis/bladder pain syndrome (IC/BPS) is a bladder pain disorder associated with voiding symptomatology and other systemic chronic pain disorders. Currently diagnosis of IC/BPS is complicated, as patients present with wide ranges of symptoms, physical examination findings, and clinical test responses. One hypothesis is that IC symptoms arise from increased bladder permeability to urine solutes. This study established the feasibility of using contrast-enhanced magnetic resonance imaging (CE-MRI) to quantify bladder permeability in IC patients. Materials and Methods Permeability alterations in bladder urothelium were assessed with intravesical administration of a MRI contrast agent (Gd-DTPA) in a small cohort of patients. MRI signal intensities (SI) in IC patient and control bladders were compared regionally and for entire bladders. Results Quantitative assessment of MRI SI indicated a significant increase in SI within anterior bladder regions (p<0.01) compared to posterior regions in IC patients, and significant increases in SI within anterior bladder regions (p<0.001) and kurtosis (descriptor of shape of probability distribution) and skewness (measure of asymmetry of probability distribution) associated with contrast enhancement in total bladders (p<0.05) for IC patients compared to controls. Regarding symptomatology, IC cases differed significantly from controls for the SF-36, PPUF and ICPI questionnaires with no overlap in range of scores for each group, and were significantly different for ICSI but with a slight overlap in range of scores. Conclusions The data suggests that CE-MRI provides an objective, quantifiable measurement of bladder permeability that could be used to stratify bladder pain patients and monitor therapy.

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Section: Discussionmentioning

confidence: 99%

A Feasibility Study to Determine Whether Clinical Contrast Enhanced Magnetic Resonance Imaging can Detect Increased Bladder Permeability in Patients with Interstitial Cystitis

Towner

Wisniewski

et al. 2016

Journal of Urology

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“…6, 37, 38 Primary antibodies: Upk1a, Upk2, Upk3b, Shh, p63 (Santa Cruz Biotechnology, Santa Cruz, CA), Upk3a (Fitzgerald Industries International, Acton, MA), Krt13, Krt5, Krt14 (Covance, Princeton, NJ), and Krt20 (Dako North America, Inc., Carpinteria, CA) were detected using Anti-Polyvalent or Anti-Goat and, HRP/DAB reagents (Scytek Laboratories, Logan, UT). Sections were imaged using an Olympus BX51 microscope and CX9000 camera.…”

Section: Methodsmentioning

confidence: 99%

Uroplakin 1b is critical in urinary tract development and urothelial differentiation and homeostasis

Carpenter

Becknell

Ching

et al. 2016

Kidney International

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Proper development and maintenance of urothelium is critical to its function. Uroplakins are expressed in developing and mature urothelium where they establish plaques associated with the permeability barrier. Their precise functional role in development and disease is unknown. Here, we disrupted Upk1b in vivo where its loss resulted in urothelial plaque disruption in the bladder and kidney. Upk1bRFP/RFP bladder urothelium appeared dysplastic with expansion of the progenitor cell markers, Krt14 and Krt5, increased Shh expression, and loss of terminal differentiation markers Krt20 and uroplakins. Upk1bRFP/RFP renal urothelium became stratified with altered cellular composition. Upk1bRFP/RFP mice developed age-dependent progressive hydronephrosis. Interestingly, 16% of Upk1bRFP/RFP mice possessed unilateral duplex kidneys. Our study expands the role of uroplakins, mechanistically links plaque formation to urinary tract development and function, and provides a tantalizing connection between congenital anomalies of the kidney and urinary tract along with functional deficits observed in a variety of urinary tract diseases. Thus, kidney and bladder urothelium are regionally distinct and remain highly plastic, capable of expansion through tissue-specific progenitor populations. Furthermore, Upk1b plays a previously unknown role in early kidney development representing a novel genetic target for congenital anomalies of the kidney and urinary tract.

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“…Trigone morphology changes as the bladder and urethra expand, increasing the distance between the ureters and urethral opening (Fig. 6F) (Carpenter et al, 2012). The ureters are muscular tubes that transport urine from the renal pelvis to the bladder ( Fig.…”

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

confidence: 99%

“…6G-J; supplementary material). The ureters are inserted in a stereotypical position in the trigone, where ureteral muscle and bladder muscle intersect to form the anti-reflux valve (Carpenter et al, 2012;Viana et al, 2007) (Fig. 6K,L).…”

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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3‐dimensional morphometric analysis of murine bladder development and dysmorphogenesis

Cited by 9 publications

References 33 publications

A Feasibility Study to Determine Whether Clinical Contrast Enhanced Magnetic Resonance Imaging can Detect Increased Bladder Permeability in Patients with Interstitial Cystitis

A Feasibility Study to Determine Whether Clinical Contrast Enhanced Magnetic Resonance Imaging can Detect Increased Bladder Permeability in Patients with Interstitial Cystitis

Uroplakin 1b is critical in urinary tract development and urothelial differentiation and homeostasis

An illustrated anatomical ontology of the developing mouse lower urogenital tract

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