Fig. 1.

Spindle positioning regulates oriented/asymmetric cell division during metazoan development. (A) Spindle orientation regulates asymmetric cell divisions in early C. elegans development. The first zygotic division produces daughter cells that are asymmetric in both size and fate specification. Prior to division, the cell cortex is polarized along an anterior-posterior (A-P) axis by the activity of PAR (blue) and PKC-3 (red). Spindle orientation is coupled to this polarity axis primarily through the action of the GPR-1/2 and LIN-5 complex (yellow/green), which enriches along the posterior cortex. In subsequent divisions, the Fz-Dsh complex (orange) regulates spindle orientation in the EMS cell. Similar to the one-cell stage, PAR complexes show reciprocal polarity in EMS and P2 cells (Arata et al., 2010), whereas GPR-1/2 influences spindle positioning through asymmetric localization in the P2 cell specifically (Werts, Roh-Johnson and Goldstein, 2011). (B) Drosophila neuroblasts polarize along an apical-basal (A-B) axis through the activity of the Par-aPKC complex (red). Spindle orientation is regulated by the apical Pins complex, which recruits the regulatory proteins Mud, Dlg and Khc-73 (yellow/green). Neuroblast asymmetric divisions result in a larger self-renewed neuroblast (NB) and a smaller ganglion mother cell (GMC), which is specified for neuronal differentiation by the inheritance of the Mira-Pros-Brat complex (blue). (C) Drosophila sensory organ precursor cells (SOPs) in the epithelium of developing wing imaginal discs give rise to the adult mechanosensory bristles. Each SOP progenitor gives rise to five distinct cells that constitute the entire bristle structure: g, glial; h, hair; n, neuron; sh, shaft; so, socket. Spindle orientation in the initial (pI) cell division is regulated by the coordinated action of Pins (green), which positions the spindle within the epithelial plane, and Fz-Dsh (orange), which regulates orientation along the A-P axis. Pins-mediated rotation of the spindle in the pIIb cell then establishes the A-B division orientation necessary for correct specification and positioning of the neuronal and glial cells. (D) In the mouse skin, basal epidermal cells (ep) divide within the epithelial plane early in development, resulting in expansion of the tissue (left). At later developmental stages (right), division orientation switches to an A-B mode via Pins-mediated repositioning of the mitotic spindle. This mode of division positions one daughter, the suprabasal (sb) cell, below the epithelium. The sb cell differentially inherits Notch, which specifies differentiation resulting in stratification of the skin.