Collective cell migration during human mammary gland organoid morphogenesis

Abstract

Organ morphogenesis is driven by cellular migration patterns, which become accessible for observation in organoid cultures. We demonstrate here that mammary gland organoids cultured from human primary cells, exhibit oscillatory and collective migration patterns during their development into highly branched structures, as well as persistent rotational motion within the developed alveoli. Using high-resolution live-cell imaging, we observed cellular movement over the course of several days and subsequently characterized the underlying migration pattern by means of optical flow algorithms. Confined by the surrounding collagen matrix, characteristic correlated back-and-forth movements emerge due to a mismatch between branch invasion and cell migration speeds throughout the branch invasion phase. In contrast, alveolar cells exhibit continuous movement in the same direction. By modulating cell-cell adhesions, we identified collective migration as a prerequisite for sustaining these migration patterns both during the branching elongation process and after alveolus maturation.