Mesenchymal-epithelial interactions in the bladder

Baskin, Laurence S.; Hayward, Simon W.; Sutherland, R. A.; DiSandro, Michael; Thomson, Axel A.; Goodman, Joseph; Cunha, Gerald R.

doi:10.1007/bf00184602

Cited by 52 publications

(42 citation statements)

References 37 publications

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“…Appropriate epithelial-mesenchymal interaction is essential for normal bladder development; in the absence of bladder epithelium, bladder smooth muscle does not develop normally (Baskin et al, 1996a). To examine how the p63-null epithelium affects the adjacent mesenchyme, we studied the expression of Msx1, a homeobox gene that is induced in the mesenchyme by an epithelium-derived signal.…”

Section: Failure Of Ventral Ugs Mesenchymal Induction and Proliferatimentioning

confidence: 99%

ΔNp63 plays an anti-apoptotic role in ventral bladder development

et al. 2006

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The bladder, the largest smooth-muscle organ in the human body, is responsible for urine storage and micturition. P63, a homolog of the p53 tumor-suppressor gene, is essential for the development of all stratified epithelia, including the bladder urothelium. The N-terminal truncated isoform of p63, ⌬Np63, is known to have anti-apoptotic characteristics. We have established that ⌬Np63 is not only the predominant isoform expressed throughout the bladder, but is also preferentially expressed in the ventral bladder urothelium during early development. We observed a host of ventral defects in p63 -/-embryos, including the absence of the abdominal and ventral bladder walls. This number of ventral defects is identical to bladder exstrophy, a congenital anomaly exhibited in human neonates. In the absence of p63, the ventral urothelium was neither committed nor differentiated, whereas the dorsal urothelium was both committed and differentiated. Furthermore, in p63 -/-bladders, apoptosis in the ventral urothelium was significantly increased. This was accompanied by the upregulation of mitochondrial apoptotic mediators Bax and Apaf1, and concurrent upregulation of p53. Overexpression of ⌬Np63␥ and ⌬Np63␤ in p63 -/-bladder primary cell cultures resulted in a rescue, evidenced by significantly reduced expressions of Bax and Apaf1. We conclude that ⌬Np63 plays a crucial anti-apoptotic role in normal bladder development.

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Section: Failure Of Ventral Ugs Mesenchymal Induction and Proliferatimentioning

confidence: 99%

ΔNp63 plays an anti-apoptotic role in ventral bladder development

et al. 2006

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“…These paracrine-signaling events orchestrate the development and functions of organs establishing morphology during organogenesis and maintaining adult differentiation. Previous studies have demonstrated that cellcell signaling between the stroma and epithelium are integral for correct bladder development (Baskin et al, 1996a(Baskin et al, ,b, 2001DiSandro et al, 1998;Liu et al, 2000;Staack et al, 2005). Studies by Baskin and co-workers have demonstrated reciprocal cellcell signaling between the stromal and epithelial compartments.…”

Section: Introductionmentioning

confidence: 98%

Bladder tissue formation from cultured bladder urothelium

Oottamasathien

Williams

Franco

et al. 2006

Developmental Dynamics

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Tissue recombination is a powerful method to evaluate the paracrine-signaling events that orchestrate the development of organs using the in vivo environment of a host rodent. Studies have reported the successful generation of primary cultures of rodent bladder urothelium, but none have reported their use to recapitulate bladder tissue with tissue recombination. We propose that primary cultured bladder urothelium, when recombined with inductive embryonic bladder mesenchyme, will form bladder tissue in a recombination model. Adult rat bladders were isolated and urothelium obtained. Sheets of bladder urothelium were re-suspended in collagen and maintained in tissue culture. After expansion (>20 passages), the urothelium was recombined with embryonic day-14 mouse bladder mesenchyme, then grafted beneath the renal capsule of immunocompromised mouse hosts. Grafts were harvested after 28 days. Control grafts were performed with bladder mesenchyme alone, cultured bladder urothelium alone, and collagen matrix alone. Final tissues were evaluated with staining and immunohistochemistry (H&E, Gomori's trichrome, broad-spectrum uroplakin, and smooth muscle actin ␣ and ␥). Immunocytochemistry on cultured urothelium for broad-spectrum keratin, vimentin, and broad-spectrum uroplakin confirmed pure populations, void of mesenchymal contaminants. Staining of recombinant grafts demonstrated bladder tissue with mature urothelium and stromal differentiation. Control tissues were void of bladder tissue formation. We have successfully demonstrated that a chimeric bladder is formed from primary cultured bladder urothelium recombined with embryonic bladder mesenchyme. This is a powerful new tool for investigating the molecular mechanisms of bladder development and disease. Future applications may include the in vitro genetic manipulation of urothelium and examining those effects on growth and development in an in vivo environment. Developmental Dynamics 235:2795-2801, 2006.

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“…The long-term results of penile-straightening Mesenchymal-epithelial interactions are necessary for normal bladder, uterine and prostatic development procedures performed in young children are not known. In adults, the incidence of impotence after correcting [21][22][23]. In the urogenital tract, mesenchyme induces and specifies patterns of epithelial morphogenesis, penile curvature is extremely low, despite the many different surgical techniques [1].…”

Section: Resultsmentioning

confidence: 99%

“…The present results show the highest density of smooth muscle was adjacent to the urethral epithelium just below the cavernosal bodies that the concept of a small strip of dorsal neurovascular bundle supplying the glans is incorrect, in that the (Figs 2b,e, 3d,4b,d). It may be that, as in the bladder, prostate and uterus, the urethral epithelium is necessary nerves completely surround the cavernosal bodies, piercing the glans not just at the 11 and 1 o'clock positions, to induce smooth muscle development in the penis [21,23]. but along the entire side of the tunica (Figs 1-4,6,7).…”

Section: Resultsmentioning

confidence: 99%

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Neuroanatomical ontogeny of the human fetal penis

Baskin¹,

Lee²,

Cunha

1997

British Journal of Urology

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Objective To determine the development of the human penis, and hence the cause of congenital anomalies, using an immunohistochemical analysis of fetal penile ontogeny. Materials and methods In 25 human fetal penile specimens (gestational age 8 to 23 weeks) various tissues were localized immunohistochemically using stains for α‐actin (smooth muscle), cytokeratin 8 and 14 (epithelium) and protein gene‐product (PGP) 9.5 (neurons). Results Nerves were identified in the penis with anti‐PGP in specimens of all ages, prominent dorsally at the 11 and 1 o’clock positions but also extending around the tunica to the junction of the corpus spongiosum and corpora cavernosa, suggesting that these structures may be injured in procedures which straighten the penis. The nerves continued into the glans on the dorsal aspect, suggesting that glans reduction in feminizing genitoplasties should be performed on the ventral aspect. Smooth muscle was first noted at 10 weeks’ gestation, with epithelial differentiation occurring in the earliest specimens studied (8 weeks’ gestation). With time, smooth muscle density was highest in the corpus spongiosum, especially between it and the corpora cavernosa. Smooth muscle also developed close to the urethral epithelium. The tunica albuginea showed consistent variations in thickness, with the mid‐dorsal 12 o’clock position being the thickest, followed by the 5 and 7 o’clock periurethral positions. Conclusion A better knowledge of penile development and of the relationship of the nerves to the corpora cavernosa is useful in the strategic design of penile straightening procedures and feminizing genitoplasties.

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Mesenchymal-epithelial interactions in the bladder

Cited by 52 publications

References 37 publications

ΔNp63 plays an anti-apoptotic role in ventral bladder development

ΔNp63 plays an anti-apoptotic role in ventral bladder development

Bladder tissue formation from cultured bladder urothelium

Neuroanatomical ontogeny of the human fetal penis

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