title: The thrombospondin repeat containing protein MIG-21 controls a left-right asymmetric Wnt signaling response in migrating C. elegans neuroblasts.
abstract: Wnt proteins are secreted signaling molecules that play a central role in development and adult tissue homeostasis. Although several Wnt signal transduction mechanisms have been described in detail, it is still largely unknown how cells are specified to adopt such different Wnt signaling responses. Here, we have used the stereotypic migration of the C. elegans Q neuroblasts as a model to study how two initially equivalent cells are instructed to activate either β-catenin dependent or independent Wnt signaling pathways to control the migration of their descendants along the anteroposterior axis. We find that the specification of this difference in Wnt signaling response is dependent on the thrombospondin repeat containing protein MIG-21, which acts together with the netrin receptor UNC-40/DCC to control an initial left-right asymmetric polarization of the Q neuroblasts. Furthermore, we show that the direction of this polarization determines the threshold for Wnt/β-catenin signaling, with posterior polarization sensitizing for activation of this pathway. We conclude that MIG-21 and UNC-40 control the asymmetry in Wnt signaling response by restricting posterior polarization to one of the two Q neuroblasts.
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
authors.forename: Teije C
authors.initials: TC
authors.lastname: Middelkoop
authors.forename: Lisa
authors.initials: L
authors.lastname: Williams
authors.forename: Pei-Tzu
authors.initials: PT
authors.lastname: Yang
authors.forename: Jeroen
authors.initials: J
authors.lastname: Luchtenberg
authors.forename: Marco C
authors.initials: MC
authors.lastname: Betist
authors.forename: Ni
authors.initials: N
authors.lastname: Ji
authors.forename: Alexander
authors.initials: A
authors.lastname: van Oudenaarden
authors.forename: Cynthia
authors.initials: C
authors.lastname: Kenyon
authors.forename: Hendrik C
authors.initials: HC
authors.lastname: Korswagen
mesh_terms: D000818:Animals; D019521:Body Patterning; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism*; D002465:Cell Movement; D016764:Cell Polarity; D005110:Extracellular Space / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D000075386:Netrin Receptors; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D019699:Thrombospondins / Q000737:chemistry; D060449:Wnt Signaling Pathway
chemical_list: D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; D000075386:Netrin Receptors; D011956:Receptors, Cell Surface; D019699:Thrombospondins; D049452:Green Fluorescent Proteins