The early activation of ovarian follicles in the mouse has been closely characterised – the oocyte at the centre of the follicle grows and the granulosa cells (GCs) that enclose it become cuboidal and proliferate within the surrounding basal lamina, eventually forming multiple layers. Despite this knowledge, however, little has been understood about how these events are controlled. Now, Kate Hardy and colleagues () use histomorphometry to address the relationship between GC proliferation and oocyte growth. By labelling cells that express the cell-cycle marker Ki67, the authors first quantify the proliferation rate of GCs, which increases dramatically as they become cuboidal. They next show that GC proliferation can occur independently of oocyte growth. GCs on the basal lamina reach a maximal packing density as the second (inner) layer of GCs starts to appear; moreover, the inner layer forms because the basal GCs change their mitotic-spindle orientation and divide inwards. On the basis of these and other results, the authors propose a model in which the basal lamina (or surrounding cells) mechanically constrains the expansion of GCs, forcing the formation of additional cell layers. This study sheds light on the mechanism of ovarian-follicle activation.
