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Related Experiment Video

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Lung epithelial branching program antagonizes alveolar differentiation.

Daniel R Chang¹, Denise Martinez Alanis, Rachel K Miller

¹Department of Pulmonary Medicine and Department of Biochemistry and Molecular Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030.

Proceedings of the National Academy of Sciences of the United States of America

|September 24, 2013

Summary

Lung development involves branching and cell differentiation. This study reveals that branching morphogenesis suppresses alveolar differentiation in mice, mediated by Kras and Sox9, impacting lung maturity and complexity.

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Area of Science:

Developmental Biology
Cell Biology
Organogenesis

Background:

Mammalian organs like lungs and kidneys have branched structures for efficient function.
Lung formation requires branching morphogenesis and alveolar differentiation, but their coordination is unclear.

Purpose of the Study:

To investigate the coordination between branching morphogenesis and alveolar differentiation in mouse lung development.
To identify molecular regulators governing the balance between these two processes.

Main Methods:

Analysis of temporal and spatial correlations between branching and differentiation.
Gain-of-function studies using hyperactive Kras.
Loss-of-function studies of SRY-box containing gene 9 (Sox9).

Main Results:

Branching morphogenesis negatively correlates with alveolar differentiation temporally, spatially, and evolutionarily.
Hyperactive Kras promotes branching and suppresses alveolar cell differentiation.
Sox9 promotes branching and inhibits premature alveolar differentiation, acting downstream of Fgf/Kras.

Conclusions:

Lung epithelial progenitors balance branching morphogenesis and alveolar differentiation.
Kras and Sox9 are dual-function regulators mediating this balance.
The branching program's delay of differentiation offers insights into lung immaturity and organ evolution.