期刊
DEVELOPMENT
卷 144, 期 23, 页码 4328-4335出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.154823
关键词
Mechanical stress; Morphogenesis; Clock; Morphodynamics
资金
- National Institutes of Health [GM083997, HL110335, HL118532, HL120142]
- Division of Civil, Mechanical and Manufacturing Innovation [CMMI-1435853]
- David and Lucile Packard Foundation
- Alfred P. Sloan Foundation
- Camille and Henry Dreyfus Foundation
- Burroughs Wellcome Fund
- Svenska Sallskapet for Medicinsk Forskning
- New Jersey Commission on Cancer Research
- March of Dimes Foundation
- Howard Hughes Medical Institute
- Div Of Civil, Mechanical, & Manufact Inn
- Directorate For Engineering [1435853] Funding Source: National Science Foundation
Mechanical forces are increasingly recognized to regulate morphogenesis, but how this is accomplished in the context of the multiple tissue types present within a developing organ remains unclear. Here, we use bioengineered 'microfluidic chest cavities' to precisely control the mechanical environment of the fetal lung. We show that transmural pressure controls airway branching morphogenesis, the frequency of airway smooth muscle contraction, and the rate of developmental maturation of the lungs, as assessed by transcriptional analyses. Time-lapse imaging reveals that branching events are synchronized across distant locations within the lung, and are preceded by long-duration waves of airway smooth muscle contraction. Higher transmural pressure decreases the interval between systemic smooth muscle contractions and increases the rate of morphogenesis of the airway epithelium. These data reveal that the mechanical properties of the microenvironment instruct crosstalk between different tissues to control the development of the embryonic lung.
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