Roles for microtubules in the proliferative and differentiated cells of stratified epithelia

Abstract

While microtubule dynamics and organization have been extensively studied invitro, both biochemically and in cultured cells, recent work has begun to extend this into tissues ex vivo and organisms in vivo. Advances in genetic tools and imaging technology have allowed studies on the dynamics, function, and organization of microtubules in the stratified epithelia of the epidermis. Here, we discuss recent work that highlights the varied roles that microtubules play in supporting epidermal function. These findings demonstrate that studying microtubules in tissues has revealed not only novel aspects of epidermal biology but also new principles of microtubule regulation.

Keywords: Centrosome; Cilia; Desmosomes; Differentiation; Epidermis; Gammatubulin; Microtubule; Skin.

Figure 1:. A Snapshot of Microtubules in a Stratified Epithelium

Basal cells form the innermost layer of the epidermis, which contains the proliferative stem cells of this tissue. These cells have radial arrays of microtubules (green) emanating from an apical centrosome (red). In addition, many of these cells have cilia (A). Basal cells differentiate and move upwards, becoming squamous. The centrosome loses its ability to organize microtubules as cells differentiate (Bi-iii). This is driven by loss of the microtubule-anchoring Nedd1/γ-TuRC complex from the centrosome. As differentiation proceeds, additional pericentriolar material is lost, though centrioles remain. As centrosomes lose MTOC activity, the microtubules becoming increasingly enriched at the cortex of the differentiated cells. This reorganization requires recruitment of a group of microtubule-associated proteins by desmosomes.

Figure 2:. Mitotic Spindle Orientation in the Epidermis

Initially, the epidermis is a simple epithelium that consists of symmetrically dividing cells. When stratification begins at e14.5, mitotic spindles begin to reorient oblique to the plane of the tissue in the basal layer, but proliferative suprabasal cells divide symmetrically within the basal plane. At this stage, these divisions are independent of the spindle orientation factor LGN (58). As stratification proceeds at e16.5, the number of cells undergoing asymmetric divisions with mitotic spindles perpendicular to the basement membrane increases. At this time, spindle orientation is dependent upon LGN. Upon reaching homeostasis in adult tissue, the number of divisions decreases and those that do occur are mostly symmetric. Stratification is maintained through the delamination of cells from the basement membrane. When homeostasis is perturbed by hyperproliferation, the percentage of asymmetric and oblique cell divisions increases and this is thought to buffer the epidermis from increased stem cell number.