Motile cilia and airway disease

Semin Cell Dev Biol. 2021 Feb:110:19-33. doi: 10.1016/j.semcdb.2020.11.007. Epub 2020 Dec 2.


A finely regulated system of airway epithelial development governs the differentiation of motile ciliated cells of the human respiratory tract, conferring the body's mucociliary clearance defence system. Human cilia dysfunction can arise through genetic mutations and this is a cause of debilitating disease morbidities that confer a greatly reduced quality of life. The inherited human motile ciliopathy disorder, primary ciliary dyskinesia (PCD), can arise from mutations in genes affecting various aspects of motile cilia structure and function through deficient production, transport and assembly of cilia motility components or through defective multiciliogenesis. Our understanding about the development of the respiratory epithelium, motile cilia biology and the implications for human pathology has expanded greatly over the past 20 years since isolation of the first PCD gene, rising to now nearly 50 genes. Systems level insights about cilia motility in health and disease have been made possible through intensive molecular and omics (genomics, transcriptomics, proteomics) research, applied in ciliate organisms and in animal and human disease modelling. Here, we review ciliated airway development and the genetic stratification that underlies PCD, for which the underlying genotype can increasingly be connected to biological mechanism and disease prognostics. Progress in this field can facilitate clinical translation of research advances, with potential for great medical impact, e.g. through improvements in ciliopathy disease diagnosis, management, family counselling and by enhancing the potential for future genetically tailored approaches to disease therapeutics.

Keywords: Airway; Cilia; Disease; Multiciliogenesis; Primary ciliary dyskinesia; Reduced generation of motile cilia; Respiratory.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Axonemal Dyneins / genetics*
  • Axonemal Dyneins / metabolism
  • Cilia / metabolism*
  • Cilia / pathology
  • Cilia / ultrastructure
  • Ciliary Motility Disorders / genetics*
  • Ciliary Motility Disorders / metabolism
  • Ciliary Motility Disorders / pathology
  • Eye Proteins / genetics*
  • Eye Proteins / metabolism
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation
  • Genotype
  • Humans
  • Inheritance Patterns
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Mutation*
  • Proteins / genetics
  • Proteins / metabolism
  • Quality of Life
  • Respiratory Mucosa / metabolism*
  • Respiratory Mucosa / pathology
  • Respiratory Mucosa / ultrastructure
  • Signal Transduction


  • DNAAF6 protein, human
  • DNAI1 protein, human
  • Eye Proteins
  • FOXJ1 protein, human
  • Forkhead Transcription Factors
  • Intracellular Signaling Peptides and Proteins
  • OFD1 protein, human
  • Proteins
  • RPGR protein, human
  • Axonemal Dyneins