Shaping the intestine: The role of cell morphology and spatial dynamics in development.

Abstract

To optimize nutrient absorption and protect against physical, chemical, and microbial threats, the small intestine undergoes extensive remodeling during embryogenesis and postnatal development to establish peristalsis, expand absorptive surface area, and modulate epithelial turnover. Each developmental stage demands precise spatiotemporal regulation of cell fate specification and positioning while simultaneously coordinating cell shape changes to drive organogenesis. This chapter examines mammalian small intestinal morphogenesis from late embryogenesis through postnatal maturation, highlighting the interplay between epithelial-mesenchymal signaling, intrinsic actomyosin dynamics, and external mechanical forces in gut tube elongation, smooth muscle patterning, villus morphogenesis, and crypt formation. Once the crypt-villus axis is established, epithelial cells employ dynamic extracellular matrix interactions and cytoskeletal reorganization to migrate toward the villus tip, where they are extruded to maintain high turnover. Insights from animal models and in vitro organoid systems reveal how tissue architecture not only emerges from but reinforces epithelial maturation and functional specialization.