Occlusion and subsequent re-canalization in early duodenal development of human embryos: integrated organogenesis and histogenesis through a possible epithelial-mesenchymal interaction

Abstract

Histogenesis of the duodenum, especially changes in the epithelium in relation to temporal occlusion and re-canalization of the lumen, was investigated by light microscopy together with morphometric analysis, as well as by scanning and transmission electron microscopy of 133 externally normal human embryos ranging from Carnegie stage 12 to 23. A series of morphogenetic events passed the duodenum in a cranio-caudal (proximo-distal) wave like fashion during the period examined. They included: (1) a decrease in the caliber and area of the lumen, (2) 'occlusion' of the lumen, (3) vacuole formation, (4) 're-canalization' and villi formation. The only exemption to this rule was that, in the upper part of the duodenum, the lumen was not obliterated in the embryos examined. Morphometric analyses revealed that both the area of the epithelium and the number of epithelial cells decreased during the 'occlusion' phase. This result suggests that, unlike the classical view, epithelial cell proliferation does not play an important role in occluding the lumen, but the predominant morphogenetic event during this phase is convergence of the epithelial cells to elongate the duodenum. Apoptosis, contrary to some classical views, decreased during the 're-canalization' phase, and it appeared to be involved in the formation of the small lumens in the epithelial 'plug' and in villi formation, but not in enlarging the secondary lumens. The secondary small lumens in the occluded lumen were frequently formed near the border between the central 'plug' and peripheral basal cells on the basement membrane. This and other findings of concentric differentiation in both the epithelial and mesenchymal layers suggested a possible control mechanism by the epithelium-mesenchymal interaction on human duodenal morphogenesis and histogenesis. The present electron microscopic observations also provided details on the mechanisms involved in the enlargement of the secondary lumen and differentiation of villi. The implications of these findings to duodenal anomalies are also discussed.

Jun N-terminal kinase maintains tissue integrity during cell rearrangement in the gut

“…Similar morphogenetic properties and processes are implicated in mammalian gut elongation, as suggested by the abnormal polarity and/or stratification of the intestinal epithelium observed in Wnt/PCP mutant mice (Cervantes et al, 2009;Matsuyama et al, 2009;Yamada et al, 2010). Moreover, the definitive (gut-forming) endoderm undergoes convergent extension rearrangements prior to formation of the gut tube (García-García et al, 2008) and it has been hypothesized that endoderm cells in the gut tube itself also rearrange in order for the tube to narrow as it lengthens (Matsumoto et al, 2002;Yamada et al, 2010). However, during later stages of development, transformation of the pseudostratified architecture of the primitive gut lining into a less densely packed mature epithelium has also been postulated to contribute to lengthening (Grosse et al, 2011).…”

Morphogenesis of the primitive gut tube is generated by Rho/ROCK/myosin II–mediated endoderm rearrangements

“…Early in human gut development, undifferentiated endoderm cells fill the core of the PGT, temporarily occluding its patency (Matsumoto et al, 2002), but as the gut lumen recanalizes, the endoderm forms a single layer of polarized epithelium that lines the gut walls. This process coincides with gut elongation, suggesting a mechanistic link between gut elongation and digestive epithelial morphogenesis (Matsumoto et al, 2002).…”

“…Early in human gut development, undifferentiated endoderm cells fill the core of the PGT, temporarily occluding its patency (Matsumoto et al, 2002), but as the gut lumen recanalizes, the endoderm forms a single layer of polarized epithelium that lines the gut walls. This process coincides with gut elongation, suggesting a mechanistic link between gut elongation and digestive epithelial morphogenesis (Matsumoto et al, 2002). In mammalian embryos, retrospective analyses suggest that cells in the developing epithelium rearrange during the elongation of the PGT (Matsumoto et al, 2002), but the nature of the putative tissue-elongating rearrangements is unknown.…”

“…This process coincides with gut elongation, suggesting a mechanistic link between gut elongation and digestive epithelial morphogenesis (Matsumoto et al, 2002). In mammalian embryos, retrospective analyses suggest that cells in the developing epithelium rearrange during the elongation of the PGT (Matsumoto et al, 2002), but the nature of the putative tissue-elongating rearrangements is unknown.…”

Stomach curvature is generated by left-right asymmetric gut morphogenesis

“…This is not surprising, as polarity is a prerequisite for cells to undergo radial rearrangement (Marsden and Desimone, 2001) and endoderm cells acquire apicobasal polarity as they rearrange to lengthen the intestine and form the mature digestive epithelium (Grosse et al, 2011;Matsumoto et al, 2002;Reed et al, 2009). In Foxj1 heterozygous mice, the endoderm of the posterior right stomach wall becomes irregularly stratified, whereas the left endoderm is highly polarized (as indicated by apical enrichment of tubulin; …”