An Ichor-dependent apical extracellular matrix regulates seamless tube shape and integrity

Abstract

During sprouting angiogenesis in the vertebrate vascular system, and primary branching in the Drosophila tracheal system, specialized tip cells direct branch outgrowth and network formation. When tip cells lumenize, they form subcellular (seamless) tubes. How these seamless tubes are made, shaped and maintained remains poorly understood. Here we characterize a Drosophila mutant called ichor (ich), and show that ich is essential for the integrity and shape of seamless tubes in tracheal terminal cells. We find that Ich regulates seamless tubulogenesis via its role in promoting the formation of a mature apical extracellular matrix (aECM) lining the lumen of the seamless tubes. We determined that ich encodes a zinc finger protein (CG11966) that acts, as a transcriptional activator required for the expression of multiple aECM factors, including a novel membrane-anchored trypsin protease (CG8213). Thus, the integrity and shape of seamless tubes are regulated by the aECM that lines their lumens.

Morphogenesis of neurons and glia within an epithelium

“…Thus, although each of the individual cells retains its apical-basal polarity, the continuous lumen from sheath to socket is lost. These defects are comparable with phenotypes seen in the C. elegans excretory system or Drosophila tracheal tubes upon disruption of apical ECM (Jazẃinśka et al, 2003;Wang et al, 2006;Stone et al, 2009;Mancuso et al, 2012;Gill et al, 2016;Forman-Rubinsky et al, 2017;Pu et al, 2017;Cohen et al, 2018;Rosa et al, 2018). Thus, amphid dendrites are shaped by interactions within an epithelium composed of neurons, glia and skin.…”

Morphogenesis of neurons and glia within an epithelium

“…In the absence of these factors, the developing tube-shaped glial pore ruptures at glial junctions and, although each of the individual cells retains its apical-basal polarity, the continuous lumen from sheath to socket is lost. These defects are comparable to phenotypes seen in the C. elegans excretory system or Drosophila tracheal tubes upon disruption of apical ECM (Jaźwińska et al, 2003;Wang et al, 2006;Stone et al, 2009;Mancuso et al, 2012;Gill et al, 2016;Forman-Rubinsky et al, 2017;Pu et al, 2017;Rosa et al, 2018). Thus, amphid dendrites are shaped by interactions within an epithelium composed of neurons, glia, and skin.…”

A multi-layered and dynamic apical extracellular matrix shapes the vulva lumen in Caenorhabditis elegans

“…Tubular epithelia drive water into the lumen by establishing ionic and osmotic gradients using various ion pumps and channels; the resulting hydrostatic pressure can stimulate lumen enlargement ( Bagnat et al, 2007 ; Dong et al, 2011 ; Khan et al, 2013 ; Kolotuev et al, 2013 ; Navis et al, 2013 ). But ions and water are not the only molecules being secreted into nascent lumens; proteoglycans, lipids, mucins, zona pellucida (ZP) domain proteins, and/or other matrix factors are also present and can contribute to lumen shaping ( Devine et al, 2005 ; Gill et al, 2016 ; Hwang et al, 2003b ; Jaźwińska et al, 2003 ; Lane et al, 1993 ; Rosa et al, 2018 ; Strilić et al, 2009 ; Tonning et al, 2005 ). These aECM factors may act like sponges to bind and organize water molecules and generate outward pushing forces ( Lane et al, 1993 ; Syed et al, 2012 ), or they may assemble into fibrils or other specialized structures to exert more localized pushing or pulling forces on tube membranes ( Andrew and Ewald, 2010 ; Linde-Medina and Marcucio, 2018 ; Luschnig and Uv, 2014 ; Plaza et al, 2010 ).…”