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.
Please note: Abstract shown here should NOT be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
The Genetics Society of America
9650 Rockville Pike, Bethesda, MD
Phone: 301-634-7300, Fax: 301-634-7079
Questions and Comments: firstname.lastname@example.org