期刊
DEVELOPMENTAL BIOLOGY
卷 409, 期 1, 页码 106-113出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2015.10.018
关键词
Cloaca; Bladder; Shh; Dkk1; HREM
资金
- NIH/NIDCR [1R01DE019823]
- NIH/NIDDK [1R01DK091645-01A1]
- Department of Urology, Boston Children's Hospital, Harvard Medical School
- Science and Technology Commission of Shanghai Municipality [12ZR1448000]
The developmental process through which the cloaca transforms from one hollow structure to two separated urinary and digestive outlets remains controversial and speculative. Here, we use high-resolution episcopic microscopy to examine a comprehensive series of normal and mutant mouse cloaca in which the detailed 3-dimensional (3-D) morphological features are illuminated throughout the development. We provide evidence that the dorsal peri-cloacal mesenchyme (dPCM) remains stationary while other surrounding tissues grow towards it. This causes dramatic changes of spatial relationship among caudal structures and morphological transformation of the cloaca. The 3-D characterizations of Dkkl mutants reveal a hyperplastic defect of dPCM, which leads to a significant anterior shift of the caudal boundary of the cloaca, premature occlusion of the cloaca and, imperforate anus phenotype. Conversely, Shh knockout causes a severe hypoplastic defect of cloaca mesenchyme including dPCM and persistent cloaca. Collectively, these findings suggest that formation of the dPCM is critical for cloaca] morphogenesis and furthermore, growth and movement of the mesenchymal tissues towards the dPCM lead to the cloaca occlusion and separation of the urinary and digestive outlets. (C) 2015 Elsevier Inc. All rights reserved.
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