Several organs develop via branching morphogenesis and, although the branching of some organs (e.g. the lung, kidney and salivary gland) is well understood, little is known about how branching occurs in mammary glands. Now, Marja Mikkola and colleagues combine optical projection tomography, time-lapse imaging and manipulation of E13.5 ex vivo cultured mammary glands, which include mesenchymal components, to provide a thorough quantitative description of embryonic mammary gland development in mice. They find that mammary branching morphogenesis occurs predominantly via lateral branching (i.e. budding off of an established branch), although terminal bifurcation (i.e. the splitting of a tip into two new branches) is also present. Branch points appear to form stochastically, leading to variable network shapes; however, because the branching frequency is relatively constant, morphogenesis progresses reliably. The authors exogenously supply signalling factors involved in postnatal branching to their ex vivo culture system to show that Fgf10 and Tgfβ1 increase or decrease branching frequency, respectively. Finally, the authors disrupt planar cell polarity by using Vangl2-knockout glands, revealing that loss of Vangl2 significantly decreases growth via prevention of main duct elongation but increases branching frequency compared with wild types. Overall, this study addresses branching morphogenesis in the embryonic mouse mammary gland at the tissue level.
