Centrosome positioning in vertebrate development

Abstract

SummaryThe centrosome, a major organizer of microtubules, has important functions in regulating cell shape, polarity, cilia formation and intracellular transport as well as the position of cellular structures, including the mitotic spindle. By means of these activities, centrosomes have important roles during animal development by regulating polarized cell behaviors, such as cell migration or neurite outgrowth, as well as mitotic spindle orientation. In recent years, the pace of discovery regarding the structure and composition of centrosomes has continuously accelerated. At the same time, functional studies have revealed the importance of centrosomes in controlling both morphogenesis and cell fate decision during tissue and organ development. Here, we review examples of centrosome and centriole positioning with a particular emphasis on vertebrate developmental systems, and discuss the roles of centrosome positioning, the cues that determine positioning and the mechanisms by which centrosomes respond to these cues. The studies reviewed here suggest that centrosome functions extend to the development of tissues and organs in vertebrates.

Acentriolar mitosis activates a p53-dependent apoptosis pathway in the mouse embryo

“…Nevertheless, we observe that specification of the anterior-posterior body axis, which requires Wnt, Nodal, BMP, and FGF signaling, is normal in the absence of centrioles and centrosomes. It has been suggested that centrosomes are important in directed cell migration (55), but the polarized collective migration of the anterior visceral endoderm (56) is normal in the absence of centrioles, as shown by the formation of a single anterior-posterior body axis in Sas4 −/− embryos. Similarly, the apical-basal oscillations of nuclei in pseudostratified epithelia (interkinetic nuclear migration) are thought to depend on an apically anchored centrosome (57), but restriction of mitotic cells to the apical surface of the neural epithelium is normal in Sas4 −/− mutants ( Fig.…”

The benefits of local depletion: The centrosome as a scaffold for ubiquitin-proteasome-mediated degradation

“…These studies also raise implications about the potential of centrosome-associated degradation in controlling subcellular organization in other contexts if additional, well-established observations of centrosome positioning are considered. Given that centrosomes have been shown to act as polarity cues in multiple systems 93,94 and tend to assume stereotyped subcellular positions in a number of differentiated cell types (epithelial cells, migrating fibroblasts), 95 it could be imagined that centrosome-associated degradation may be used as a strategy to locally deplete polarity-determining factors from certain subcellular domains in order to contribute to intracellular organization.…”

Small regulators, major consequences – Ca2+ and cholesterol at the endosome–ER interface

“…As cholesterol is released from LDL in the acidic environment of late endosomes, cholesterol might act as maturation signal that induces the transport of mature endosomes towards the minus ends of microtubules [which are typically organized by a microtubule-organizing center (MTOC)]. In non-polarized cells, the MTOC is located adjacent to the nucleus in the center of the cell (Tang and Marshall, 2012). Increases in late endosomal cholesterol allow recruitment of the dynein motor and transport towards the MTOC, and therefore the transport of mature endosomes deeper into cells.…”