Curvature feedback for repetitive tissue morphogenesis – Bridging algorithmic principles and self-regulatory systems

Abstract

Tissue patterning during organ development consists of intricate morphogenetic processes, driven by the interplay of physical and genetic cues among constituent cells. Despite its complexity, these processes can be decomposed into fundamental morphogenetic motifs that appear repeatedly in a spatiotemporally organized manner, giving rise to diverse organ architectures. Recent studies have highlighted tissue-scale curvature as critical information for constitutive cells, which enables it to bridge mechanical and biochemical signals. In this review, we discuss the regulatory principles underlying the roles of tissue curvature in morphogenesis along with recent insights from earlier studies. Here, we focus on the dual role of tissue curvature as an instructive signal that directs collective cell behavior and as a dynamic property modulated by cellular activities. First, we introduce the concept of morphogenetic motifs and provide examples from developmental processes in various organ systems. Next, we discuss how cells collectively respond to two distinct curvature types, lateral and topographical, and examine the mechanisms by which cells sense these curvatures from a mechanobiological perspective. Finally, we highlight the repetitive terminal bifurcation in developing murine lung epithelium, illustrating how curvature-driven feedback loops, mediated through mechano-chemical multicellular couplings, ensure robust morphogenetic cycles. By integrating geometric, mechanical, and chemical cues, curvature feedback emerges as a framework for self-organized morphogenesis, providing fresh perspectives on the recurrent properties and robustness of development.