Center for Molecular and Human Genetics, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America.
PLoS One. 2013;8(1):e53675. doi: 10.1371/journal.pone.0053675. Epub 2013 Jan 7.
In this study, we examined the expression of Sonic Hedgehog, Patched, Gli1, Gli2, Gli3 and Myocardin in the developing bladders of male and female normal and megabladder (mgb-/-) mutant mice at embryonic days 12 through 16 by in situ hybridization. This analysis indicated that each member of the Sonic Hedgehog signaling pathway as well as Myocardin displayed distinct temporal and spatial patterns of expression during normal bladder development. In contrast, mgb-/- bladders showed both temporal and spatial changes in the expression of Patched, Gli1 and Gli3 as well as a complete lack of Myocardin expression. These changes occurred primarily in the outer mesenchyme of developing mgb-/- bladders consistent with the development of an amuscular bladder phenotype in these animals. These results provide the first comprehensive analysis of the Sonic Hedgehog signaling pathway during normal bladder development and provide strong evidence that this key signaling cascade is critical in establishing radial patterning in the developing bladder. In addition, the lack of detrusor smooth muscle development observed in mgb-/- mice is associated with bladder-specific temporospatial changes in Sonic Hedgehog signaling coupled with a lack of Myocardin expression that appears to result in altered patterning of the outer mesenchyme and poor initiation and differentiation of smooth muscle cells within this region of the developing bladder.
在这项研究中，我们通过原位杂交技术研究了 Sonic Hedgehog、Patched、Gli1、Gli2、Gli3 和 Myocardin 在正常和巨膀胱（mgb-/-）突变雄性和雌性小鼠胚胎第 12 至 16 天发育过程中的表达。这项分析表明， Sonic Hedgehog 信号通路的每个成员以及 Myocardin 在正常膀胱发育过程中均表现出独特的时空表达模式。相比之下，mgb-/-膀胱在 Patched、Gli1 和 Gli3 的表达以及 Myocardin 表达完全缺失方面均表现出时空变化。这些变化主要发生在发育中的 mgb-/-膀胱的外间充质中，与这些动物中出现的无肌肉膀胱表型的发育一致。这些结果提供了 Sonic Hedgehog 信号通路在正常膀胱发育过程中的首次全面分析，并提供了强有力的证据表明，这个关键信号级联对于建立发育中膀胱的放射状模式至关重要。此外，在 mgb-/-小鼠中观察到的逼尿肌平滑肌发育缺失与 Sonic Hedgehog 信号的膀胱特异性时空变化相关，同时缺乏 Myocardin 表达，这似乎导致了外间充质的图案改变以及发育中膀胱该区域平滑肌细胞的启动和分化不良。
