Abstract
In multicellular organisms, epithelial cells are key elements of tissue organization. In developing tissues, cellular proliferation and differentiation are under the tight regulation of morphogenetic programs, that ensure the correct organ formation and functioning. In these processes, mitotic rates and division orientation are crucial in regulating the velocity and the timing of the forming tissue. Division orientation, specified by mitotic spindle placement with respect to epithelial apico-basal polarity, controls not only the partitioning of cellular components but also the positioning of the daughter cells within the tissue, and hence the contacts that daughter cells retain with the surrounding microenvironment. Daughter cells positioning is important to determine signal sensing and fate, and therefore the final function of the developing organ. In this review, we will discuss recent discoveries regarding the mechanistics of planar divisions in mammalian epithelial cells, summarizing technologies and model systems used to study oriented cell divisions in vitro such as three-dimensional cysts of immortalized cells and intestinal organoids. We also highlight how misorientation is corrected in vivo and in vitro, and how it might contribute to the onset of pathological conditions.
Highlights
The mitotic spindle is a bipolar structure formed by microtubules (MTs) that in mitosis captures the duplicated chromosomes and segregates them between daughter cells
We summarize what is known about mitotic spindle dynamics and oriented cell divisions in vertebrate 3D cysts and organoids
In hepatocytes, that in addition to apico-basal polarity organize a lateral lumen for the development of bile canalicular networks and have reduced Rho activity, Par1b prevents NuMA/ LGN lateral recruitment causing tilted spindles and asymmetric partitioning of the lateral lumen among daughter cells (LázaroDiéguez et al, 2013; Slim et al, 2013). In addition to their cohesive role, some junctional proteins have been shown to be involved in spindle orientation in cysts, including the Junctional adhesion molecule-A (JAM-A), Afadin (AF6), E-Cadherin and Dlg-1 (Discs large homolog 1) (Figure 1B)
Summary
The mitotic spindle is a bipolar structure formed by microtubules (MTs) that in mitosis captures the duplicated chromosomes and segregates them between daughter cells. In hepatocytes, that in addition to apico-basal polarity organize a lateral lumen for the development of bile canalicular networks and have reduced Rho activity, Par1b prevents NuMA/ LGN lateral recruitment causing tilted spindles and asymmetric partitioning of the lateral lumen among daughter cells (LázaroDiéguez et al, 2013; Slim et al, 2013) In addition to their cohesive role, some junctional proteins have been shown to be involved in spindle orientation in cysts, including the Junctional adhesion molecule-A (JAM-A), Afadin (AF6), E-Cadherin and Dlg-1 (Discs large homolog 1) (Figure 1B). JAM-A was shown to activate Cdc in progenitors of the developing cerebral cortex this way contributing to spindle orientation (Fededa et al, 2016)
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