Unicellular tubes with an intracellular lumen are found in the mammalian microvasculature and in some invertebrate organs, including the C. elegans excretory (renal-like) system. Many unicellular tubes are seamless –they lack autocellular junctions along their length – and they adopt elongated or branched shapes. How cells become seamless tubes with such complex shapes is poorly understood. We’ve shown that the C. elegans excretory duct forms a seamless tube by cell wrapping to form an autocellular junction, followed by membrane fusion to remove that junction and become a seamless toroid. The duct tube subsequently elongates more than five-fold and adopts an unusual asymmetric shape. Seamlessness and tube shape depend on the EGF-Ras-ERK signaling cascade. Surprisingly, we found that signaling promotes both seamlessness and elongated tube shape via a single downstream target, the plasma membrane fusogen AFF-1.
Using transcriptional reporters for aff-1, we demonstrated that EGF-Ras-ERK signaling promotes aff-1 expression in the duct cell through a combination of relief of LIN-1/Ets-dependent repression and stimulation of LIN-1/Ets + EOR-1/BTB-Zn finger-dependent activation. Although duct auto-fusion occurs at the 1.5-fold stage of embryogenesis, aff-1 expression in the duct persists throughout much of larval development. In the absence of aff-1, the duct retains an autocellular junction and has a dramatically shortened morphology, with the lumen only ~a third of its normal length. Furthermore, lumen markers accumulate in a diffuse pattern adjacent to the main lumen, suggesting possible accumulation of a vesicular intermediate. Continuous expression of aff-1 cDNA in the duct cell rescues auto-fusion and tube morphogenesis, while late expression can rescue a part of the duct shape and lumen phenotypes independently of auto-fusion. Our results suggest a continuous role for AFF-1 in seamless tube morphogenesis, and reveal an unexpected link between fusogen activity and intracellular lumen elongation.
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