Spatiotemporal mapping of vascularization and innervation in the fetal murine intestine

Abstract

Background: In mice, the intestinal tube develops from the splanchopleure before embryonic day 9.5. Subsequent patterning of nerves and blood vessels is critical for normal digestive function. A hierarchical branching vascular network allows for efficient nutrient absorption, while the complex enteric nervous system regulates intestinal motility as well as secretion, absorption, and blood flow. Despite the well-recognized significance of these systems, the precise mechanisms by which they develop have not been clearly established in mammals. Results: Using a novel whole-mount immunohistochemical protocol, we visualize the pattern of intestinal neurovascular development in mice between embryonic day 10.5 and birth. In particular, we focus on the development and remodeling of the enteric vascular plexus, the migration and organization of enteric neural crest-derived cells, and the integration of peripheral sympathetic nerves with the enteric nervous system. These correlative data lead us to hypothesize a functional interaction between migrating neural crest-derived cells and endothelial cells of the primary capillary plexus, as well as a subsequent interaction between developing peripheral autonomic nerves and differentiated neural crest-derived cells. Conclusions: These studies provide useful anatomical data for continuing investigations on the functional mechanisms underlying intestinal organogenesis. Developmental Dynamics 244:56-68, 2015. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Vascular and neural stem cells in the gut: do they need each other?

“…Nishiyama et al (2012) showed that the major part of the colonic ENS is colonized via transmesenteric routes. In a recent study, it could be demonstrated that primary vascularization is required for NCCs migration, which never enter a region of the gut before the capillary plexus is developed (Hatch and Mukouyama 2014).…”

Mesenchymal–epithelial interactions during digestive tract development and epithelial stem cell regeneration

“…During development, the digestive mesenchyme is colonized by vENCCs, endothelial and lymphatic cells [147][148][149][150]. Unexpectedly, the number of vENCCs contributes to the maintenance of stomach identity and differentiation through inhibition of the Notch signaling pathway [72].…”

“…This demonstrates that by regulating mesenchyme identity, vENCCs act as a new mediator of mesenchymal-epithelial interactions in the control of gastric epithelial regionalization. The close association of endothelial and lymphatic cells with ENCCs during the establishment of their respective networks and also in adults [148][149][150] opens the way for investigating new potential actors in the regulation of mesenchymal-epithelial interactions during development, but also in adults. Besides smooth muscle, enteric and endothelial cells, the GI wall contains many other cell types (for instance, fibroblasts, lymphocytes and leukocytes) [124] that could be involved in mesenchymal-epithelial interaction mechanisms to maintain the regionalization and homeostasis of digestive epithelia in adults.…”

Pluripotent stem cell-derived organoids: using principles of developmental biology to grow human tissues in a dish

“…In the embryo, developing endodermal and mesodermal organs also become innervated, and these peripheral nerves are required for function of the adult organ (Aven and Ai, 2013;Hatch and Mukouyama, 2015;Pichel et al, 1996). For example, the intestine contains 500 million neurons, and these all derive from neural crest cells that migrate into the gut mesenchyme shortly after gut tube formation.…”