Cell shape controls mitotic orientation. (A) Drawing by O. Hertwig of the confined frog embryo after its first division illustrating Hertwig’s rule. The image was scanned by Google Docs from Hertwig (1893). (B) Without apparent interactions with the cell boundary, we might expect the small mitotic spindle in a large cell to position randomly, but it orients according to Hertwig’s rule. This image was adapted from Wühr et al. (2009). (C and D) Micropatterned fibronectin in various geometries results in well-defined mitotic orientations (C) determined by actin-rich retraction fibers (D; green). blue, DNA; arrowheads, positions of spindle poles. (E) Computational modeling predicts the expected orientation based on adhesion pattern shape. C–E are reprinted from Théry et al., 2007 with permission from Nature Publishing Group.