MRCK controls myosin II activation in the polarized cortex of mouse oocytes and promotes spindle rotation and male pronucleus centration

Abstract

AbstractAsymmetric meiotic divisions in oocytes rely on spindle positioning in close vicinity to the cortex. In mouse oocytes arrested at metaphase II, eccentric spindle positioning is associated with a chromatin-induced remodeling of the overlying cortex, including the build-up of an actin cap surrounded by a ring of activated myosin II. While the role of the actin cap in promoting polar body formation was demonstrated, the role of ring myosin II, and its mechanism of activation, have remained elusive. Here, we show that ring myosin II activation requires Myotonic dystrophy kinase-Related Cdc42-binding Kinase (MRCK), downstream of polarized Cdc42. During anaphase-II, inhibition of MRCK resulted in spindle rotation defects and a decreased rate of polar body emission. Remarkably, some oocytes eventually achieved spindle rotation by disengaging one cluster of chromatids from the anaphase spindle. We show that the MRCK/myosin II pathway also regulates the flattening of the fertilization cone to initiate male pronucleus centration. These findings provide novel insights into mammalian oocyte polarization and the role of cortical myosin II in orchestrating asymmetric division.