RT Journal Article
SR Electronic
T1 Maternal expression of the novel centrosome assembly factor Wdr8 is required for vertebrate embryonic mitosis and development
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 031336
DO 10.1101/031336
A1 Daigo Inoue
A1 Manuel Stemmer
A1 Thomas Thumberger
A1 Joachim Wittbrodt
A1 Oliver J. Gruss
YR 2015
UL http://biorxiv.org/content/early/2015/11/12/031336.abstract
AB The assembly of the first centrosome occurs upon fertilisation when the male centrioles recruit pericentriolar material (PCM) from the egg cytoplasm. While inaccuracy in the assembly of centrosomes leads to infertility and abnormal embryogenesis, the mechanism that ensures accurate assembly in vertebrate embryos remains obscure. Here we applied a CRISPR-Cas9-mediated gene knockout to show that Wdr8, a novel centrosomal protein, is maternally essential for PCM assembly during embryonic mitoses of medaka (Oryzias latipes). Maternal/zygotic Wdr8-null (Wdr8−/−) blastomeres exhibit severe defects in PCM assembly that cause them to divide asymmetrically and develop multipolar mitotic spindles and aneuploidy. We demonstrate that Wdr8 interacts via its WD40 domains with the centriolar satellite protein SSX2IP. Strikingly, exogenously provided Wdr8 fully rescues Wdr8−/− embryos to adulthood, except in variants with mutations in the WD40 domains. This combination of targeted gene inactivation and in vivo reconstitution of the maternally essential Wdr8-SSX2IP complex reveals an essential link between maternal PCM and the stability of the zygotic genome in the early vertebrate embryo.