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It’s about time: clocks in the developing lung
Colleen M. Bartman, … , Aleksey Matveyenko, Y.S. Prakash
Colleen M. Bartman, … , Aleksey Matveyenko, Y.S. Prakash
Published January 2, 2020
Citation Information: J Clin Invest. 2020;130(1):39-50. https://doi.org/10.1172/JCI130143.
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Review

It’s about time: clocks in the developing lung

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Abstract

The discovery of peripheral intracellular clocks revealed circadian oscillations of clock genes and their targets in all cell types, including those in the lung, sparking exploration of clocks in lung disease pathophysiology. While the focus has been on the role of these clocks in adult airway diseases, clock biology is also likely to be important in perinatal lung development, where it has received far less attention. Historically, fetal circadian rhythms have been considered irrelevant owing to lack of external light exposure, but more recent insights into peripheral clock biology raise questions of clock emergence, its concordance with tissue-specific structure/function, the interdependence of clock synchrony and functionality in perinatal lung development, and the possibility of lung clocks in priming the fetus for postnatal life. Understanding the perinatal molecular clock may unravel mechanistic targets for chronic airway disease across the lifespan. With current research providing more questions than answers, it is about time to investigate clocks in the developing lung.

Authors

Colleen M. Bartman, Aleksey Matveyenko, Y.S. Prakash

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Figure 2

Timeline of five stages of lung development in mice and humans and the potential role of the clock.

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Timeline of five stages of lung development in mice and humans and the p...
The five milestones of lung development are embryonic (formation of lung buds), pseudoglandular (branching morphogenesis), canalicular (formation of epithelial sacs and appearance of capillaries), saccular (production of alveolar ducts and surfactant protein), and alveolar (maturation of the alveoli). Mouse stages are represented in embryonic (E) or postnatal (P) days, and human stages are represented by post-conception weeks (pcw). One potential role of the clock includes regulation of clock gene expression dependent on cell type specificity and differentiation during developmental stages with coordinated oscillations postnatally. Alternatively, the clock may be involved in prenatal priming for adaptation to postnatal life. In the latter model, insults like premature birth and necessary interventions deleteriously affect the clock and drive progression of chronic airway disease.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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