Mesenchymal Vangl1 and Vangl2 facilitate airway elongation and widening independently of the planar cell polarity complex.

Adult mammalian lungs exhibit a fractal pattern, as each successive generation of airways is a fraction of the size of the parental branch. Achieving this structure likely requires precise control of airway length and diameter, as the embryonic airways initially lack the fractal scaling observed in the adult. In monolayers and tubes, directional growth can be regulated by the planar cell polarity (PCP) complex.

Vangl-dependent mesenchymal thinning shapes the distal lung during murine sacculation.

The planar cell polarity (PCP) complex is speculated to function in murine lung development, where branching morphogenesis generates an epithelial tree whose distal tips expand dramatically during sacculation. Here, we show that PCP is dispensable in the airway epithelium for sacculation. Rather, we find a Celsr1-independent role for the PCP component Vangl in the pulmonary mesenchyme: loss of Vangl1/2 inhibits mesenchymal thinning and expansion of the saccular epithelium.

Mesenchymal facilitates airway elongation and widening independently of the planar cell polarity complex.

A hallmark of mammalian lungs is the fractal nature of the bronchial tree. In the adult, each successive generation of airways is a fraction of the size of the parental branch. This fractal structure is physiologically beneficial, as it minimizes the energy needed for breathing.

How to build an epithelial tree.

Nature has evolved a variety of mechanisms to build epithelial trees of diverse architectures within different organs and across species. Epithelial trees are elaborated through branch initiation and extension, and their morphogenesis ends with branch termination. Each of these steps of the branching process can be driven by the actions of epithelial cells themselves (epithelial-intrinsic mechanisms) or by the cells of their surrounding tissues (epithelial-extrinsic mechanisms).

New mouse models for high resolution and live imaging of planar cell polarity proteins in vivo.

The collective polarization of cellular structures and behaviors across a tissue plane is a near universal feature of epithelia known as planar cell polarity (PCP). This property is controlled by the core PCP pathway, which consists of highly conserved membrane-associated protein complexes that localize asymmetrically at cell junctions. Here, we introduce three new mouse models for investigating the localization and dynamics of transmembrane PCP proteins: Celsr1, Fz6 and Vangl2.

Exploiting codon usage identifies intensity-specific modifiers of Ras/MAPK signaling in vivo.

Signal transduction pathways are intricately fine-tuned to accomplish diverse biological processes. An example is the conserved Ras/mitogen-activated-protein-kinase (MAPK) pathway, which exhibits context-dependent signaling output dynamics and regulation. Here, by altering codon usage as a novel platform to control signaling output, we screened the Drosophila genome for modifiers specific to either weak or strong Ras-driven eye phenotypes.

Interleukin-13 disrupts type 2 pneumocyte stem cell activity.

The T helper 2 (Th2) inflammatory cytokine interleukin-13 (IL-13) has been associated with both obstructive and fibrotic lung diseases; however, its specific effect on the epithelial stem cells in the gas exchange compartment of the lung (alveolar space) has not been explored. Here, we used in vivo lung models of homeostasis and repair, ex vivo organoid platforms, and potentially novel quantitative proteomic techniques to show that IL-13 disrupts the self-renewal and differentiation of both murine and human type 2 alveolar epithelial cells (AEC2s). Significantly, we find that IL-13 promotes ectopic expression of markers typically associated with bronchiolar airway cells and commonly seen in the alveolar region of lung tissue from patients with idiopathic pulmonary fibrosis.

Indispensable pre-mitotic endocycles promote aneuploidy in the Drosophila rectum.

The endocycle is a modified cell cycle that lacks M phase. Endocycles are well known for enabling continued growth of post-mitotic tissues. By contrast, we discovered pre-mitotic endocycles in precursors of Drosophila rectal papillae (papillar cells).