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Dev Biol. 2016 Jan 1;409(1):106-113. doi: 10.1016/j.ydbio.2015.10.018. Epub 2015 Oct 17.

Clarification of mammalian cloacal morphogenesis using high-resolution episcopic microscopy.

Author information

1
Departments of Urology and Pathology, Boston Children's Hospital, and Department of Surgery, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
2
Department of Urology, Shanghai Children's Hospital, Shanghai JiaoTong University, Shanghai 200062, China.
3
Departments of Urology and Pathology, Boston Children's Hospital, and Department of Surgery, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA. Electronic address: sean.li@childrens.harvard.edu.

Abstract

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 Dkk1 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 cloacal 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.

KEYWORDS:

Bladder; Cloaca; Dkk1; HREM; Shh

PMID:
26485363
PMCID:
PMC4688061
DOI:
10.1016/j.ydbio.2015.10.018
[Indexed for MEDLINE]
Free PMC Article

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