title: Maternal Dead-End1 is required for vegetal cortical microtubule assembly during Xenopus axis specification.
abstract: Vertebrate axis specification is an evolutionarily conserved developmental process that relies on asymmetric activation of Wnt signaling and subsequent organizer formation on the future dorsal side of the embryo. Although roles of Wnt signaling during organizer formation have been studied extensively, it is unclear how the Wnt pathway is asymmetrically activated. In Xenopus and zebrafish, the Wnt pathway is triggered by dorsal determinants, which are translocated from the vegetal pole to the future dorsal side of the embryo shortly after fertilization. The transport of dorsal determinants requires a unique microtubule network formed in the vegetal cortex shortly after fertilization. However, molecular mechanisms governing the formation of vegetal cortical microtubule arrays are not fully understood. Here we report that Dead-End 1 (Dnd1), an RNA-binding protein required for primordial germ cell development during later stages of embryogenesis, is essential for Xenopus axis specification. We show that knockdown of maternal Dnd1 specifically interferes with the formation of vegetal cortical microtubules. This, in turn, impairs translocation of dorsal determinants, the initiation of Wnt signaling, organizer formation, and ultimately results in ventralized embryos. Furthermore, we found that Dnd1 binds to a uridine-rich sequence in the 3'-UTR of trim36, a vegetally localized maternal RNA essential for vegetal cortical microtubule assembly. Dnd1 anchors trim36 to the vegetal cortex in the egg, promoting high concentrations of Trim36 protein there. Our work thus demonstrates a novel and surprising function for Dnd1 during early development and provides an important link between Dnd1, mRNA localization, the microtubule cytoskeleton and axis specification.
authors.affiliation: Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, 3411 Veterinary Medicine Basic Sciences Building, Urbana, IL 61802, USA.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Mei
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Jin
authors.forename: Fangfang
authors.initials: F
authors.lastname: Lai
authors.forename: Tyler
authors.initials: T
authors.lastname: Schwend
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Houston
authors.forename: Mary Lou
authors.initials: ML
authors.lastname: King
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D019521:Body Patterning; D002352:Carrier Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D047908:Intracellular Signaling Peptides and Proteins; D018613:Microscopy, Confocal; D008870:Microtubules / Q000502:physiology*; D011401:Promoter Regions, Genetic; D016601:RNA-Binding Proteins / Q000235:genetics*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism; D014981:Xenopus / Q000196:embryology* / Q000235:genetics; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D000070584:Tripartite Motif Proteins
chemical_list: D020413:3' Untranslated Regions; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016601:RNA-Binding Proteins; D051153:Wnt Proteins; D029867:Xenopus Proteins; C000624414:Dnd1 protein, Xenopus; C534481:Trim36 protein, Xenopus; D044767:Ubiquitin-Protein Ligases; D000070584:Tripartite Motif Proteins
keywords: Axis specification; Cortical rotation; Dnd1; Microtubules; Xenopus