REVIEW article
Front. Cardiovasc. Med.
Sec. Cardiovascular Genetics and Systems Medicine
This article is part of the Research TopicNew Insights in Rare Genes Involved in Inherited Cardiac DiseasesView all 9 articles
Broadening Horizons: New Links Between Cilia and Heart Development and Disease
Provisionally accepted
- 1Lanzhou University, Lanzhou, China
- 2Lanzhou University First Hospital, Lanzhou, China
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Congenital heart disease (CHD) is the most common birth defect, and its pathogenesis is closely related to the abnormal establishment of the left-right (LR) body axis, which highly depends on the ciliary function of the left-right organizer (LRO). This review systematically expounds the molecular pathways by which ciliary structural and functional abnormalities cause cardiac malformations by integrating multi-species model evidence. We believe that defects in multiple conserved genes (including CFAP45, ZIC3, FOXJ1, NEK3, APLNR, and microRNAs) disrupt ciliary assembly, motility, or signaling capacity, leading to the disappearance of the leftward nodal flow or mechanical sensing failure within the LRO. This further interrupts the left-specific calcium ion flicker and the activation of the Nodal-Pitx2 signaling cascade, ultimately resulting in failed cardiac looping and structural defects (such as ventricular septal defect and transposition of the great arteries). This review integrates transcriptional regulation, protein stability, miRNA-mediated fine regulation, and the planar cell polarity (PCP) pathway into a unified "cilia-LRO-heart" network and explores the molecular mechanisms of cilia in valve diseases and cardiac fibrosis. This not only deepens the understanding of the fundamental biological processes of heart development but also provides new molecular targets and theoretical frameworks for the genetic diagnosis and counseling of related congenital heart diseases.
Keywords: Cilia, cardiovascular disease, congenital heart defects, Gene mutations, Heart Valves, Fibrosis, heterotaxy
Received: 04 Sep 2025; Accepted: 23 Jan 2026.
Copyright: © 2026 Ma, Zhang, Ma and Ma. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Chengxu Ma
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