Abstract
The division of the embryonic cloaca is the most essential event for the formation of digestive and urinary tracts. The defective development of the cloaca results in anorectal malformations (ARMs; 2–5 per 10,000 live births). However, the developmental and pathogenic mechanisms of ARMs are unclear. In the current study, we visualized the epithelia in the developing cloaca and nephric ducts (NDs). Systemic stereoscopic analyses revealed that the ND-cloaca connection sites shifted from the lateral-middle to dorsal-anterior part of the cloaca during cloacal division from E10.5 to E11.5 in mouse embryos. Genetic cell labeling analyses revealed that the cells in the ventral cloacal epithelium in the early stages rarely contributed to the dorsal part. Moreover, we revealed the possible morphogenetic movement of endodermal cells within the anterior part of the urogenital sinus and hindgut. These results provide the basis for understanding both cloacal development and the ARM pathogenesis.
Highlights
To these two URS-based models, it has alternatively been proposed that cloacal division is achieved by descent of the dorsal cloaca to the tailgroove rather than the development of the URS30
ICR females were crossed with ShhCreERT2/+; R26LacZ/LacZ males and analyzed at E11.5, E12.75 and E14.5 subsequent to TM treatment at E9.5 (Fig. 1c–e, c’-e’)
The lateral views of X-gal-stained embryos showed cloacal division processes including development of the “URS”, which is the unstained region between the anterior part of the urogenital sinus (UGS) and hindgut (Fig. 1b, c red arrows)
Summary
To these two URS-based models, it has alternatively been proposed that cloacal division is achieved by descent of the dorsal cloaca to the tailgroove rather than the development of the URS30. A recent analysis suggested that oriented cell division in the cloacal epithelium is essential for cloacal separation[33]. There have been several discussions on the development of the cloaca, stereoscopic analyses are rarely utilized. The time-course analysis visualized the division processes of the cloaca. A series of BrdU incorporation assays, including a pulse-chase analysis, suggested the presence of possible remodeling and different dorsoventral characteristics in the cloacal epithelium. These results may contribute to the understanding of the physiology of cloacal development, thereby providing the basis for the pathogenic mechanisms of ARMs
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