Analysis of Genetic Strategies for Targeting Embryonic Airway Smooth Muscle

20 Pages Posted: 16 Aug 2022

See all articles by Katharine Goodwin

Katharine Goodwin

Princeton University - Lewis-Sigler Institute for Integrative Genomics

Celeste M. Nelson

Princeton University - Department of Chemical and Biological Engineering

Abstract

During development of the embryonic mouse lung, the pulmonary mesenchyme differentiates into smooth muscle that wraps around the airway epithelium. Inhibiting smooth muscle differentiation leads to cystic airways, while enhancing it stunts epithelial branching. These findings support a conceptual model wherein the differentiation of smooth muscle sculpts the growing epithelium into branches at precise positions and with stereotyped morphologies. Unfortunately, most approaches to manipulate the differentiation of airway smooth muscle rely on pharmacological or physical perturbations that are conducted ex vivo . Here, we explored the use of diphtheria toxin-based genetic ablation strategies to eliminate airway smooth muscle in the embryonic mouse lung. Surprisingly, neither airway smooth muscle wrapping nor epithelial branching were affected in embryos in which the expression of diphtheria toxin or its receptor were driven by several different smooth muscle-specific Cre lines. Close examination of spatial patterns of Cre activity in the embryonic lung revealed that none of these commonly used Cre lines target embryonic airway smooth muscle robustly or specifically. Our findings demonstrate the need for airway smooth muscle-specific Cre lines that are active in the embryonic lung, and serve as a useful resource for researchers contemplating the use of these commonly used Cre lines for studying embryonic airway smooth muscle.

Keywords: mechanical stress, morphodynamics, Morphogenesis

Suggested Citation

Goodwin, Katharine and Nelson, Celeste M., Analysis of Genetic Strategies for Targeting Embryonic Airway Smooth Muscle. Available at SSRN: https://ssrn.com/abstract=4191741 or http://dx.doi.org/10.2139/ssrn.4191741

Katharine Goodwin

Princeton University - Lewis-Sigler Institute for Integrative Genomics ( email )

Celeste M. Nelson (Contact Author)

Princeton University - Department of Chemical and Biological Engineering ( email )

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