Rebuilding MTOCs upon centriole loss during mouse oogenesis

Abstract

The vast majority of animal cells contain canonical centrosomes as a main microtubule-organizing center defined by a central pair of centrioles. As a rare and striking exception to this rule, vertebrate oocytes loose their centrioles at an early step of oogenesis. At the end of oogenesis, centrosomes are eventually replaced by numerous acentriolar microtubule-organizing centers (MTOCs) that shape the spindle poles during meiotic divisions. The mechanisms involved in centrosome and acentriolar MTOCs metabolism in oocytes have not been elucidated yet. In addition, little is known about microtubule organization and its impact on intracellular architecture during the oocyte growth phase following centrosome disassembly. We have investigated this question in the mouse by coupling immunofluorescence and live-imaging approaches. We show that growing oocytes contain dispersed pericentriolar material, responsible for microtubule assembly and distribution all over the cell. The gradual enlargement of PCM foci eventually leads in competent oocytes to the formation of big perinuclear MTOCs and to the assembly of large microtubule asters emanating from the close vicinity of the nucleus. Upon meiosis resumption, perinuclear MTOCs spread around the nuclear envelope, which in parallel is remodelled before breaking-down, via a MT- and dynein-dependent mechanism. Only fully competent oocytes are able to perform this dramatic reorganization at NEBD. Therefore, the MTOC-MT reorganization that we describe is one of key feature of mouse oocyte competency.

Error-prone meiotic division and subfertility in mice with oocyte-conditional knockdown of pericentrin

“…Pcnt −/− mice show a similar pathology to MOPDII with significant in utero growth restriction and developmental defects that can lead to embryonic lethality (Chen et al, 2014). Pcnt is expressed in mouse oocytes, where it localizes specifically to aMTOCs during oocyte growth and throughout the progression of meiotic division (Łuksza et al, 2013;Ma and Viveiros, 2014;Schuh and Ellenberg, 2007). Our previous in vitro studies indicate that Pcnt functions as a scaffolding protein in mouse oocytes analogous to its role in mitotic cells, whereby it regulates the accumulation of essential proteins, such as γ-tubulin and the γ-tubulin ring complex (γTuRC)-associated protein Nedd1, at aMTOCs during meiotic division (Ma et al, 2010;Ma and Viveiros, 2014).…”

Functional specialization of chordate CDK1 paralogs during oogenic meiosis

“…In this case, acentriolar MTOCs coordinate asymmetric cell divisions producing oocyte polar bodies. [18][19][20] To our knowledge, the presence of CDK1 on meiotic centrosomes has not been directly demonstrated. Nonetheless, protein kinase B, implicated in the initial activation of CDK1 in mouse oocytes, has been found to localize to acentriolar meiotic centrosomes.…”

Centriolin, a centriole-appendage protein, regulates peripheral spindle migration and asymmetric division in mouse meiotic oocytes

“…During oogenesis, an oocyte loses its centrioles, and the meiotic spindle is organized in the absence of typical centrosomes. 12 In mouse oocytes, meiotic spindles are organized by the assembly of numerous small asters that gather at the acentriolar spindle poles. 2 It is well known that centrosome components such as g-tubulin, pericentrin, and the nuclear mitotic apparatus (NuMA) protein participate in meiotic spindle organization in oocytes.…”