Regulation of asymmetric cell division in the epidermis

Abstract

For proper tissue morphogenesis, cell divisions and cell fate decisions must be tightly and coordinately regulated. One elegant way to accomplish this is to couple them with asymmetric cell divisions. Progenitor cells in the developing epidermis undergo both symmetric and asymmetric cell divisions to balance surface area growth with the generation of differentiated cell layers. Here we review the molecular machinery implicated in controlling asymmetric cell division. In addition, we discuss the ability of epidermal progenitors to choose between symmetric and asymmetric divisions and the key regulatory points that control this decision.

Figure 1

Asymmetric division of epidermal progenitor cells through perpendicular spindle orientation promotes stratification. (A) Epidermis is a multi-layered structure whose inner most layer, the basal layer (BL), contains progenitor cells that can orient their mitotic spindle parallel or perpendicular to the underlying basement membrane (BM) to undergo symmetric (SCD) or asymmetric division (ACD) respectively. Asymmetric division of a basal cell gives rise to a differentiated suprabasal/spinous layer (SL) cell and a proliferative basal cell. Cells of the SL further differentiate and migrate outward to give rise to the granular layer (GL) and the cornified layer (CL). (B) Coupling between the apical Par polarity complex and NuMA in mitosis is proposed to direct apical-basal spindle orientation to drive ACD in the epidermal basal cells.

Figure 2

Robust control of perpendicular spindle orientation in epidermal basal cells. Wild-type cells expressing intrinsic ACD factors like mInsc localize mInsc/LGN/NuMA at the apical cortex in early mitosis but do not establish stable perpendicular spindle until late metaphase. As described in text, recent results have showed that spindle orientation can be regulated downstream of Insc/LGN recruitment by regulating NuMA maintenance at the apical end. Thus cells have mechanisms for robust regulation of mitotic spindle orientation to ensure optimum balance between SCD and ACD. Such mechanisms might help to respond quickly to extrinsic cues or intrinsic imbalances.