title: Morphogenesis of the C. elegans Intestine Involves Axon Guidance Genes.
abstract: Genetic and molecular studies have provided considerable insight into how various tissue progenitors are specified in early embryogenesis, but much less is known about how those progenitors create three-dimensional tissues and organs. The C. elegans intestine provides a simple system for studying how a single progenitor, the E blastomere, builds an epithelial tube of 20 cells. As the E descendants divide, they form a primordium that transitions between different shapes over time. We used cell contours, traced from confocal optical z-stacks, to build a 3D graphic reconstruction of intestine development. The reconstruction revealed several new aspects of morphogenesis that extend and clarify previous observations. The first 8 E descendants form a plane of four right cells and four left cells; the plane arises through oriented cell divisions and VANG-1/Van Gogh-dependent repositioning of any non-planar cells. LIN-12/Notch signaling affects the left cells in the E8 primordium, and initiates later asymmetry in cell packing. The next few stages involve cell repositioning and intercalation events that shuttle cells to their final positions, like shifting blocks in a Rubik's cube. Repositioning involves breaking and replacing specific adhesive contacts, and some of these events involve EFN-4/Ephrin, MAB-20/semaphorin-2a, and SAX-3/Robo. Once cells in the primordium align along a common axis and in the correct order, cells at the anterior end rotate clockwise around the axis of the intestine. The anterior rotation appears to align segments of the developing lumen into a continuous structure, and requires the secreted ligand UNC-6/netrin, the receptor UNC-40/DCC, and an interacting protein called MADD-2. Previous studies showed that rotation requires a second round of LIN-12/Notch signaling in cells on the right side of the primordium, and we show that MADD-2-GFP appears to be downregulated in those cells.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Alparsan
authors.initials: A
authors.lastname: Asan
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Raiders
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.|Molecular and Cellular Biology Program, University of Washington, Seattle, Washington, United States of America.|Department of Biology, University of Washington, Seattle, Washington, United States of America.
authors.forename: James R
authors.initials: JR
authors.lastname: Priess
mesh_terms: D000818:Animals; D001369:Axons; D017173:Caenorhabditis elegans / Q000196:embryology*; D016764:Cell Polarity; D007422:Intestines / Q000033:anatomy & histology / Q000166:cytology / Q000196:embryology*; D009024:Morphogenesis / Q000235:genetics*