title: Lack of phosphomannomutase 2 affects Xenopus laevis morphogenesis and the non-canonical Wnt5a/Ror2 signalling.
abstract: Reduced phosphomannomutase 2 activity in man leads to hypoglycosylation of glycoconjugates causing PMM2-CDG, the most common type of congenital disorders of glycosylation. Here we show that an antisense morpholino-mediated knockdown of the Xenopus laevis phosphomannomutase 2 gene provoked a general underglycosylation in frog embryos, which led to an altered phenotype and reduced glycosylation of Wnt5a as member of the non-canonical Wnt signalling. Loss of function experiments in hemi-sectioned embryos proved that due to the phosphomannomutase 2 knockdown expression of the Wnt5a/Ror2 target gene paraxial protocadherin was significantly decreased. Regarding the expression of paraxial protocadherin, a gain of function could only be achieved by injections of wnt5a and ror2 in dorsal neighbouring blastomeres, while a parallel injection of phosphomannomutase 2 morpholino led to a significant reduced level of expression. Our data show for the first time that a knockdown of phosphomannomutase 2 influences in vivo the non-canonical Wnt signalling during early embryogenesis.
authors.affiliation: Center for Child- and Adolescent Medicine and Center for Metabolic Diseases Heidelberg, Department I, Im Neuenheimer Feld 669, 69120, Heidelberg, Germany.
authors.forename: Nastassja
authors.initials: N
authors.lastname: Himmelreich
authors.affiliation: Institute of Human Genetics, Division of Developmental Genetics, University of Heidelberg, Im Neuenheimer Feld 366, 69120, Heidelberg, Germany.
authors.forename: Lilian T
authors.initials: LT
authors.lastname: Kaufmann
authors.affiliation: Institute of Human Genetics, Division of Developmental Genetics, University of Heidelberg, Im Neuenheimer Feld 366, 69120, Heidelberg, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Steinbeisser
authors.affiliation: Center for Child- and Adolescent Medicine and Center for Metabolic Diseases Heidelberg, Department I, Im Neuenheimer Feld 669, 69120, Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Körner
authors.affiliation: Center for Child- and Adolescent Medicine and Center for Metabolic Diseases Heidelberg, Department I, Im Neuenheimer Feld 669, 69120, Heidelberg, Germany. Christian.Thiel@med.uni-heidelberg.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Thiel
mesh_terms: D000818:Animals; D055785:Gene Knockdown Techniques; D009024:Morphogenesis / Q000235:genetics*; D017875:Phosphotransferases (Phosphomutases) / Q000235:genetics*; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics*; D000071818:Wnt-5a Protein; D029867:Xenopus Proteins / Q000235:genetics; D014982:Xenopus laevis
chemical_list: D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C085096:Wnt5a protein, Xenopus; D029867:Xenopus Proteins; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; C000598273:Ror2 protein, Xenopus; D017875:Phosphotransferases (Phosphomutases); C052799:phosphomannomutase