Clarification of mammalian cloacal morphogenesis using high-resolution episcopic microscopy
Yi Chen Huang1, Fang Chen2, Xue Li1
1Departments of Urology and Pathology, Boston Children's Hospital, and Department of Surgery, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Developmental Biology
|October 21, 2015
Summary
Cloacal development involves dorsal peri-cloacal mesenchyme (dPCM) growth. This study reveals dPCM
Area of Science:
- Developmental Biology
- Morphogenesis
- Genetics
Background:
- The transformation of the cloaca into separate urinary and digestive tracts is poorly understood.
- Previous models of cloacal development are controversial and lack detailed 3-D morphological data.
Purpose of the Study:
- To elucidate the developmental mechanisms of cloacal morphogenesis using high-resolution 3-D imaging.
- To investigate the role of dorsal peri-cloacal mesenchyme (dPCM) in cloacal septation.
Main Methods:
- High-resolution episcopic microscopy was employed to analyze normal and mutant mouse cloaca development.
- Detailed 3-D morphological characterization across various developmental stages.
- Analysis of Dkk1 and Shh mutant mouse models to assess genetic contributions.
Main Results:
- The dorsal peri-cloacal mesenchyme (dPCM) acts as a stationary anchor, with surrounding tissues growing towards it.
- Dkk1 mutants exhibit dPCM hyperplasia, leading to anterior cloacal boundary shift, premature occlusion, and imperforate anus.
- Shh knockout results in dPCM hypoplasia and persistent cloaca, indicating a critical role in mesenchymal development.
Conclusions:
- Formation and growth of the dPCM are essential for normal cloacal morphogenesis and septation.
- Tissue dynamics, specifically mesenchymal growth towards the dPCM, drive cloacal occlusion and outlet separation.
- Genetic defects in dPCM development (e.g., Dkk1, Shh mutations) lead to severe congenital anomalies.
