Tubulogenesis is essential for the formation and function of internal organs. One such organ is the trachea, which allows gas exchange between the external environment and the lungs. However, the cellular and molecular mechanisms underlying tracheal tube development remain poorly understood. Here, we show that the potassium channel KCNJ13 is a critical modulator of tracheal tubulogenesis. We identify Kcnj13 in an ethylnitrosourea forward genetic screen for regulators of mouse respiratory organ development. Kcnj13 mutants exhibit a shorter trachea as well as defective smooth muscle (SM) cell alignment and polarity. KCNJ13 is essential to maintain ion homeostasis in tracheal SM cells, which is required for actin polymerization. This process appears to be mediated, at least in part, through activation of the actin regulator AKT, as pharmacological increase of AKT phosphorylation ameliorates the Kcnj13-mutant trachea phenotypes. These results provide insight into the role of ion homeostasis in cytoskeletal organization during tubulogenesis.

Tubulogenesis is essential for the formation and function of internal organs. One such 49 organ is the trachea, which allows gas exchange between the external environment and 50 the lungs. However, the cellular and molecular mechanisms underlying tracheal tube 51 development remain poorly understood. Here, we show that the potassium channel 52 KCNJ13 is a critical modulator of tracheal tubulogenesis. We identify Kcnj13 in an 53 ethylnitrosourea forward genetic screen for regulators of mouse respiratory organ 54 development. Kcnj13 mutants exhibit a shorter trachea as well as defective smooth 55 muscle (SM) cell alignment and polarity. KCNJ13 is essential to maintain ion 56 homeostasis in tracheal SM cells, which is required for actin polymerization. This 57 process appears to be mediated, at least in part, through activation of the actin regulator 58 AKT, as pharmacological increase of AKT phosphorylation ameliorates the Kcnj13 59 mutant trachea phenotypes. These results provide insights into the role of ion 60 homeostasis in cytoskeletal organization during tubulogenesis. 61 62

Alice McGushin and colleagues argue for recognition of the diverse ways in which climate change affects adolescent wellbeing and call for health professionals to work with them to respond to the crisis

No abstract