Repulsive cues combined with physical barriers and cell–cell adhesion determine progenitor cell positioning during organogenesis

Azadeh Paksa, Jan Bandemer, Burkhard Hoeckendorf, Nitzan Razin, Katsiaryna Tarbashevich, Sofia Minina, Dana Meyen, Antonio Biundo, Sebastian A. Leidel, Nadine Peyrieras, Nir S. Gov, Philipp J. Keller, Erez Raz

The precise positioning of organ progenitor cells constitutes an essential, yet poorly understood step during organogenesis. Using primordial germ cells that participate in gonad formation, we present the developmental mechanisms maintaining a motile progenitor cell population at the site where the organ develops. Employing high-resolution live-cell microscopy, we find that repulsive cues coupled with physical barriers confine the cells to the correct bilateral positions. This analysis revealed that cell polarity changes on interaction with the physical barrier and that the establishment of compact clusters involves increased cell-cell interaction time. Using particle-based simulations, we demonstrate the role of reflecting barriers, from which cells turn away on contact, and the importance of proper cell-cell adhesion level for maintaining the tight cell clusters and their correct positioning at the target region. The combination of these developmental and cellular mechanisms prevents organ fusion, controls organ positioning and is thus critical for its proper function.