Negative Transpulmonary Pressure Disrupts Airway Morphogenesis by Suppressing Fgf10.

Mechanical forces are increasingly recognized as important determinants of cell and tissue phenotype and also appear to play a critical role in organ development. During the fetal stages of lung morphogenesis, the pressure of the fluid within the lumen of the airways is higher than that within the chest cavity, resulting in a positive transpulmonary pressure. Several congenital defects decrease or reverse transpulmonary pressure across the developing airways and are associated with a reduced number of branches and a correspondingly underdeveloped lung that is insufficient for gas exchange after birth.

Inhibitory morphogens and monopodial branching of the embryonic chicken lung.

Background: Branching morphogenesis generates a diverse array of epithelial patterns, including dichotomous and monopodial geometries. Dichotomous branching can be instructed by concentration gradients of epithelial-derived inhibitory morphogens, including transforming growth factor-β (TGFβ), which is responsible for ramification of the pubertal mammary gland. Here, we investigated the role of autocrine inhibitory morphogens in monopodial branching morphogenesis of the embryonic chicken lung.

Loss of junctophilin-3 contributes to Huntington disease-like 2 pathogenesis.

Objective: Huntington disease-like 2 (HDL2) is a progressive, late onset autosomal dominant neurodegenerative disorder, with remarkable similarities to Huntington disease (HD). HDL2 is caused by a CTG/CAG repeat expansion. In the CTG orientation, the repeat is located within the alternatively spliced exon 2A of junctophilin-3 (JPH3), potentially encoding polyleucine and polyalanine, whereas on the strand antisense to JPH3, the repeat is in frame to encode polyglutamine.

Mammary branch initiation and extension are inhibited by separate pathways downstream of TGFβ in culture.

During the branching morphogenesis process that builds epithelial trees, signaling from stimulatory and inhibitory growth factors is integrated to control branch initiation and extension into the surrounding stroma. Here, we examined the relative roles played by these stimulatory and inhibitory signals in the patterning of branch initiation and extension of model mammary epithelial tubules in culture. We found that although several growth factors could stimulate branching, they did not determine the sites at which new branches formed or the lengths to which branches extended.

Adipose stroma induces branching morphogenesis of engineered epithelial tubules.

The mammary gland and other treelike organs develop their characteristic fractal geometries through branching morphogenesis, a process in which the epithelium bifurcates and invades into the surrounding stroma. Controlling the pattern of branching is critical for engineering these organs. In vivo, the branching process is instructed by stromal-epithelial interactions and adipocytes form the largest component of the fatty stroma that surrounds the mammary epithelium.