A Guide Toward Multi-scale and Quantitative Branching Analysis in the Mammary Gland

• Published in: Cell Migration in Three Dimensions Vol. 2608; pp. 183 - 205
• Main Authors: Hannezo, Edouard, Scheele, Colinda L. G. J.
• Format: Book Chapter Journal Article
• Language: English
• Published: New York, NY Springer US 2023
• Series: Methods in Molecular Biology
• Subjects: Animals; Biophysical modeling; Branching morphogenesis; Cell Lineage; Clonal lineage tracing; Epithelial Cells; Mammary gland; Mammary Glands, Animal; Morphogenesis - genetics; Stem cell fate choices; Whole-mount imaging; Whole-mount imaging; Biophysical modeling; Branching morphogenesis; Stem cell fate choices; Clonal lineage tracing; Mammary gland
• ISBN: 9781071628867; 1071628860
• ISSN: 1064-3745; 1940-6029
• DOI: 10.1007/978-1-0716-2887-4_12

The mammary gland consists of a bilayered epithelial structure with an extensively branched morphology. The majority of this epithelial tree is laid down during puberty, during which actively proliferating terminal end buds repeatedly elongate and bifurcate to form the basic structure of the ductal tree. Mammary ducts consist of a basal and luminal cell layer with a multitude of identified sub-lineages within both layers. The understanding of how these different cell lineages are cooperatively driving branching morphogenesis is a problem of crossing multiple scales, as this requires information on the macroscopic branched structure of the gland, as well as data on single-cell dynamics driving the morphogenic program. Here we describe a method to combine genetic lineage tracing with whole-gland branching analysis. Quantitative data on the global organ structure can be used to derive a model for mammary gland branching morphogenesis and provide a backbone on which the dynamics of individual cell lineages can be simulated and compared to lineage-tracing approaches. Eventually, these quantitative models and experiments allow to understand the couplings between the macroscopic shape of the mammary gland and the underlying single-cell dynamics driving branching morphogenesis.