Morphogenesis and maturation of the embryonic and postnatal intestine

Abstract

The intestine is a vital organ responsible for nutrient absorption, bile and waste excretion, and a major site of host immunity. In order to keep up with daily demands, the intestine has evolved a mechanism to expand the absorptive surface area by undergoing a morphogenetic process to generate finger-like units called villi. These villi house specialized cell types critical for both absorbing nutrients from food, and for protecting the host from commensal and pathogenic microbes present in the adult gut. In this review, we will discuss mechanisms that coordinate intestinal development, growth, and maturation of the small intestine, starting from the formation of the early gut tube, through villus morphogenesis and into early postnatal life when the intestine must adapt to the acquisition of nutrients through food intake, and to interactions with microbes.

Keywords: Endoderm; Intestine; Morphogenesis; Organoid; Villus.

Figure 1. The adult epithelial crypt-villus unit

The adult intestinal epithelium is arranged in crypt-villus units. Intestinal stem cells (ISCs) and Paneth cells are housed in the crypt. A Transit Amplifying (TA) zone is a site for rapid proliferation and amplification of undifferentiated progenitor cells as they begin to make cell fate choices. Differentiated cell types continue to move up the villus in a conveyer-belt fashion where they carry out their day-to-day function, until they reach the villus tip where they undergo apoptosis and slough off into the lumen. Villus cell types include enterocytes, goblet cells and enteroendocrine cells, as well as enterochromafin cells, tuft cells and M-cells (not shown).

Figure 2. Developmental epithelial transitions and mesenchymal cluster formation in the mouse intestine

A. The early murine intestinal epithelium (yellow), between E9.5-E13.5, is present as a flat pseudostratified epithelium within the gut tube. B. Beginning around E14.5, mesenchymal clusters (red) aggregate adjacent to the epithelium where a nascent villus will form. Cluster formation causes a deformation in the epithelium above the cluster. C. Villi form above the cluster, establishing the highly proliferative intervillus domain between villi. Several rounds of villus morphogenesis will occur, and new clusters will form (blue) adjacent to the intervillus domain following completion of the prior round of cluster-villus formation (red clusters).

Figure 3. Human fetal intestine development

Sections through different Carnegie Stages (CS) of the developing human embryo were obtained (http://www.3dembryoatlas.com and de Bakker et al., 2016) and traces of the proximal small intestine (duodenum) were generated. The intestinal epithelium (yellow) appeared to have multiple lumens prior to villus morphogenesis (CS18), and nascent villi formation was apparent by CS20. Image resolution was not sufficient to determine if the human intestine formed villus clusters in the mesenchyme (red). Villus structures became more pronounced, and greater in number as development progressed (CS21–CS23).