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Primary cilia in gut development and diseases
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DOI：10.1016/j.gendis.2026.102389.png)
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Abstract
En 中文
Primary cilia are highly specialized signaling organelles that play essential roles in coordinating gastrointestinal development, homeostasis, and disease. Recent studies demonstrate that ciliary architecture, established through centrosome maturation, intraflagellar transport, and transition zone gating, creates a unique signaling compartment that organizes pathways such as Hedgehog signaling. During gut development, primary cilia on epithelial, mesenchymal, and smooth muscle cells regulate intestinal elongation, villus morphogenesis, and stromal and neural patterning. Spatiotemporal mapping reveals that cilia are broadly distributed during embryogenesis but become largely restricted to mesenchymal and smooth muscle populations after birth, with rare epithelial cilia marking BMI1-positive reserve stem cells in adult intestinal crypts. Genetic disruption of key ciliogenesis components, including CILK1, B9D1, INPP5E, TCTN3, and TALPID3, results in intestinal shortening, villus abnormalities, and disorganized stromal architecture, highlighting the developmental dependence on cilia-mediated signaling. In adult tissues, dynamic regulation of ciliary structure contributes to epithelial turnover, metabolic adaptation, and tissue homeostasis, whereas pathological loss or aberrant re-emergence of primary cilia is implicated in congenital gut malformations, inflammatory bowel disease, and colorectal cancer. Collectively, these findings establish the gastrointestinal tract as a cilia-regulated organ system and identify ciliary signaling as a promising framework for mechanistic insight and therapeutic exploration.
Keywords:
Ciliopathies
Colorectal cancer
Ciliary dynamics
Gut development
Inflammatory bowel disease
Intestinal morphogenesis
Primary cilia
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