Figure 2.

Regulation of MBR inheritance at the cell-population and single-cell levels. (A) Simplified model of MBR retention at the cell-population level. When the area of the cells falls below a threshold (discontinuous line), cells continue dividing and generating new midbody remnants that move to the cell center and enable ciliogenesis. Successive cycles of cell division increase the number of MBR-bearing cells exponentially. The remaining fraction of cells without an MBR could be kept to generate a small pool of non-ciliated cells or be extruded from the cell monolayer. (B) Role of CHPM4C in MBR retention. A membranous stalk physically connects the MBR membrane and the plasma membranes of most MBR-containing cells. The stalk is derived from the uncleaved arm of the bridge and contains ESCRT machinery, including the regulatory subunit CHMP4C. CHMP4C acts on the second cut of the bridge membrane to preserve the MBR membrane connected to the plasma membrane. The integrity of the connection is necessary at the single-cell level to enable the centrosome to form a primary cilium. The change from tensile to compressive forces might act on CHMP4C in some way to prevent the cleavage of the second MB arm, allowing the connected MBRs to be inherited. (C) Schematics of the proposed evolutionary process leading to cilium emergence. (a) The intercellular bridge acquired microtubule-like filaments during prokaryotic-to-eukaryotic cell evolution. A primitive remnant containing this type of filament originated after the daughter cells separate. (b) The membrane of the remnant progressively acquired receptors and specialized lipids and formed a sensory patch. (c) A primordial microtubule-like organizing center emerged near the patch to nucleate microtubule-like filaments that, with the emergence of molecular motors, served as tracks for vectorial transport to the patch. (d) Microtubules replaced the microtubule-like filaments. The MTOC and the bridge remnant co-evolved in a basal body and an MBR, respectively. (e) The basal body acted as template for the formation of the axoneme, and the patch became the ciliary membrane. Since it was no longer necessary for it to remain at the plasma membrane, the MBR was discarded after the cilium had been assembled. At the beginning of the evolutionary process, both daughter cells probably inherited part of the bridge as a remnant. The acquisition of ESCRT machinery later on during evolution enabled MBR inheritance regulation. The discontinuous line indicates the transition between microtubule-like filaments and microtubules. (D) The three microtubule-based organelles and the cell cycle. The centrosome functions as a basal body in the cilium when cells are in the G0 phase, and is repurposed as the major MTOC when the cilium is disassembled and the cell returns to the cell cycle. It distributes to the poles of the mitotic spindle during the M phase. Once mitosis ends, with the formation of two identical nuclei, the MB forms to divide the cytoplasm into two halves, and gives rise to the MBR when the process of abscission is completed. Cells enter the G1 phase with the centrosome and the MBR in readiness to become engaged in primary cilium assembly.