title: Analysis of the Sonic Hedgehog signaling pathway in normal and abnormal bladder development.
abstract: 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.
authors: Center for Molecular and Human Genetics, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America. kristin.desouza@nationwidechildrens.org
authors: Kristin R
authors: KR
authors: DeSouza
authors: Monalee
authors: M
authors: Saha
authors: Ashley R
authors: AR
authors: Carpenter
authors: Melissa
authors: M
authors: Scott
authors: Kirk M
authors: KM
authors: McHugh
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D002454:Cell Differentiation; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D008297:Male; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009130:Muscle, Smooth / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics; D000072079:Patched Receptors; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics; D001743:Urinary Bladder / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism*; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3; D000099251:Myocardin
chemical_list: D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D000072079:Patched Receptors; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3; D000099251:Myocardin; C498520:Gli1 protein, mouse; C000618551:Gli2 protein, mouse; C465571:Gli3 protein, mouse; C465570:Shh protein, mouse