Spindle Formation in the Mouse Embryo Requires Plk4 in the Absence of Centrioles

Abstract

SummaryDuring the first five rounds of cell division in the mouse embryo, spindles assemble in the absence of centrioles. Spindle formation initiates around chromosomes, but the microtubule nucleating process remains unclear. Here we demonstrate that Plk4, a protein kinase known as a master regulator of centriole formation, is also essential for spindle assembly in the absence of centrioles. Depletion of maternal Plk4 prevents nucleation and growth of microtubules and results in monopolar spindle formation. This leads to cytokinesis failure and, consequently, developmental arrest. We show that Plk4 function depends on its kinase activity and its partner protein, Cep152. Moreover, tethering Cep152 to cellular membranes sequesters Plk4 and is sufficient to trigger spindle assembly from ectopic membranous sites. Thus, the Plk4-Cep152 complex has an unexpected role in promoting microtubule nucleation in the vicinity of chromosomes to mediate bipolar spindle formation in the absence of centrioles.

Polo-Like Kinases in Colorectal Cancer: Potential for Targeted Therapy

“…Embryonic lethal at E7.5 [24] -↑ In late mitotic arrest siPlk4-treated embryos [88] -Defect in spindle assembly and microtubule nucleation (Fig. 2d, e).…”

Once and only once: mechanisms of centriole duplication and their deregulation in disease

“…Although cell division can proceed in the absence of centrosomes in some circumstances 130–132 , centrosomes are generally required for sustained proliferation of mammalian cells. Mouse embryos lacking centrioles undergo widespread p53-dependent apoptosis at an earlier developmental stage than mutants that lack cilia 133 .…”

“…At present, studies that have examined the effect of centrosome amplification in mammals interfere with PLK4 expression. However, PLK4 also plays a critical role in spindle assembly in the absence of centrioles in the early mouse embyro 132 , and recent work also suggested PLK4 can control cancer cell migration and invasion through regulation of the actin cytoskeleton 201 . It will be important, therefore, to further explore these non-canonical functions of PLK4 and extend previous studies by employing alternative means to modify centriole numbers.…”

Dual spindle formation in zygotes keeps parental genomes apart in early mammalian embryos

“…Based on analysis in fixed embryos and low resolution live imaging, it was so far assumed that a single bipolar microtubule system assembles around both parental genomes (Fitzharris 2009, Courtois, Schuh et al 2012, Coelho, Bury et al 2013) that jointly congresses and biorients both sets of parental chromosomes, similar to the self-assembly of one large bipolar system that occurs in mammalian oocytes (Schuh and Ellenberg 2007, Kitajima, Ohsugi et al 2011, Holubcova, Blayney et al 2015. However, due to the extreme light-sensitivity of the mammalian embryo, previous studies could not capture the details of the dynamic process of zygotic spindle assembly.…”