Programmed cell fusion in development and homeostasis

During multicellular organism development, complex structures are sculpted to form organs and tissues, which are maintained throughout adulthood. Many of these processes require cells to fuse with one another, or with themselves. These plasma membrane fusions merge endoplasmic cellular content across external, exoplasmic, space. In the nematode Caenorhabditis elegans, such cell fusions serve as a unique sculpting force, involved in the embryonic morphogenesis of the skin-like multinuclear hypodermal cells, but also in refining delicate structures, such as valve openings and the tip of the tail. During post-embryonic development, plasma membrane fusions continue to shape complex neuron structures and organs such as the vulva, while during adulthood fusion participates in cell and tissue repair. These processes rely on two fusion proteins (fusogens): EFF-1 and AFF-1, which are part of a broader family of structurally related membrane fusion proteins, encompassing sexual reproduction, viral infection, and tissue remodeling. The established capabilities of these exoplasmic fusogens are further expanded by new findings involving EFF-1 and AFF-1 in endocytic vesicle fission and phagosome sealing. Tight regulation by cell-autonomous and non-cell autonomous mechanisms orchestrates these diverse cell fusions at the correct place and time—these processes and their significance are discussed in this review.