Increased stiffness in the tumor microenvironment generates forces on cells that promote cancer development. A signaling circuit is identified through which cells sense and respond to these changes. Patients whose tumors express these genes exhibit a better overall survival prognosis.

The mammary gland is a bilayered structure, comprising outer myoepithelial and inner luminal epithelial cells. Presented is a protocol to prepare organoids using differential trypsinization. This efficient method allows researchers to separately manipulate these two cell types to explore questions concerning their roles in mammary gland form and function.

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Amelogenesis, the formation of dental enamel, is driven by specialized epithelial cells called ameloblasts, which undergo successive stages of differentiation. Ameloblasts secrete enamel matrix proteins (EMPs), proteases, calcium, and phosphate ions in a stage-specific manner to form mature tooth enamel. Developmental defects in tooth enamel are common in humans, and they can greatly impact the well-being of affected individuals. Our understanding of amelogenesis and developmental pathologies is rooted in past studies using epithelial Cre driver and knockout alleles. However, the available mouse models are limited, as most do not allow targeting different ameloblast subpopulations, and constitutive loss of EMPs often results in severe phenotype in the mineral, making it difficult to interpret defect mechanisms. Herein, we report on the de-sign and verification of a toolkit of twelve mouse alleles that include ameloblast-stage specific Cre recombinases, fluorescent reporter alleles, and conditional flox alleles for the major EMPs. We show how these models may be used for applications such as sorting of live stage specific ameloblasts, whole mount imaging, and experiments with incisor explants.

In the mammary gland, how alveolar progenitor cells are recruited to fuel tissue growth with each estrus cycle and pregnancy remains poorly understood. Here, we identify a regulatory pathway that controls alveolar progenitor differentiation and lactation by governing Notch activation in mouse. Loss of Robo1 in the mammary gland epithelium activates Notch signaling, which expands the alveolar progenitor cell population at the expense of alveolar differentiation, resulting in compromised lactation. ROBO1 is expressed in both luminal and basal cells, but loss of Robo1 in basal cells results in the luminal differentiation defect. In the basal compartment, ROBO1 inhibits the expression of Notch ligand Jag1 by regulating β-catenin (CTNNB1), which binds the Jag1 promoter. Together, our studies reveal how ROBO1/CTTNB1/JAG1 signaling in the basal compartment exerts paracrine control of Notch signaling in the luminal compartment to regulate alveolar differentiation during pregnancy.