Work

Cilk1 Is Essential for Mesenchymal Cilia Maintenance and Epithelial-mesenchymal Crosstalk in Intestinal Villus Morphogenesis

Year: 2025

Type: article

Abstract: BACKGROUND & AIMS: Intestinal development is intricately governed by epithelial-mesenchymal crosstalk, with Hedgehog (Hh) signaling playing a pivotal role. The formation of mesenchymal clusters, driven by epithelial Hh signals, is critical for villus morphogenesis. However, the specific role of primary cilia within the mesenchyme during this process remains insufficiently understood. Ciliogenesis-associated kinase 1 (Cilk1) is crucial for maintaining primary cilia required for Hh signal transduction. This study examines the role of Cilk1 in mesenchymal ciliogenesis and cluster formation during intestinal development. METHODS: ). Postnatal deletion experiments validated Hh responsiveness in postnatal intestinal mesenchyme. RESULTS: intestines, consistent with the multi-pathway disruption identified by RNA-seq. Postnatal deletion experiments confirmed that Cilk1 is required for Hh responsiveness in postnatal intestinal mesenchyme. CONCLUSIONS: Cilk1 is essential for maintaining mesenchymal primary cilia and ensuring effective signaling required for intestinal villus morphogenesis. Disruption of Cilk1 impairs Hh-mediated mesenchymal clustering, with additional effects on BMP and Wnt pathways contributing to the developmental defects. These findings establish the critical role of Cilk1-dependent mesenchymal ciliogenesis in epithelial-mesenchymal communication during intestinal development.

Source: Cellular and Molecular Gastroenterology and Hepatology

DOI: 10.1016/j.jcmgh.2025.101672

Authors: Jieun Song, Suyeon Je, Bawool Lee, Hyuk Wan Ko

Institutions: Yonsei University, Ajou University

Language: English

Topic: Genetic and Kidney Cyst Diseases

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,430