Intestinal epithelial cell polarity defects in disease: lessons from microvillus inclusion disease

The intestinal epithelium is a highly organized tissue. The establishment
of epithelial cell polarity, with distinct apical and basolateral plasma
membrane domains, is pivotal for both barrier formation and for the
uptake and vectorial transport of nutrients. The establishment of cell
polarity requires a specialized subcellular machinery to transport and
recycle proteins to their appropriate location. In order to understand
and treat polarity-associated diseases, it is necessary to understand
epithelial cell-specific trafficking mechanisms. In this Review, we focus
on cell polarity in the adult mammalian intestine. We discuss how
intestinal epithelial polarity is established and maintained, and
how disturbances in the trafficking machinery can lead to a polarityassociated
disorder, microvillus inclusion disease (MVID). Furthermore,
we discuss the recent developments in studying MVID, including the
creation of genetically manipulated cell lines, mouse models and
intestinal organoids, and their uses in basic and applied research.