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Lack of phosphomannomutase 2 affects Xenopus laevis morphogenesis and the non-canonical Wnt5a/Ror2 signalling

  • Original Article
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Journal of Inherited Metabolic Disease

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.

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Acknowledgments

We dedicate this work to Herbert Steinbeisser and Christian Körner, who initiated and shaped this project, but could not live to see its outcome. This work was supported by a grant of the Else Kröner-Fresenius-Stiftung to CK and CT (AZ: 2010 A89).

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All institutional and national guidelines for the care and use of laboratory animals were followed.

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Authors and Affiliations

  1. Center for Child- and Adolescent Medicine and Center for Metabolic Diseases Heidelberg, Department I, Im Neuenheimer Feld 669, 69120, Heidelberg, Germany

    Nastassja Himmelreich, Christian Körner & Christian Thiel

  2. Institute of Human Genetics, Division of Developmental Genetics, University of Heidelberg, Im Neuenheimer Feld 366, 69120, Heidelberg, Germany

    Lilian T. Kaufmann & Herbert Steinbeisser

Authors
  1. Nastassja Himmelreich
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  2. Lilian T. Kaufmann
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  3. Herbert Steinbeisser
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  4. Christian Körner
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  5. Christian Thiel
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Corresponding author

Correspondence to Christian Thiel.

Additional information

Communicated by: Jaak Jaeken

Herbert Steinbeisser and Christian Körner were deceased

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ESM 1

Pmm2 identification in Xenopus laevis (Himmelreich et al Supplemental Fig. 1.pdf) (DOCX 261 kb)

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Himmelreich, N., Kaufmann, L.T., Steinbeisser, H. et al. Lack of phosphomannomutase 2 affects Xenopus laevis morphogenesis and the non-canonical Wnt5a/Ror2 signalling. J Inherit Metab Dis 38, 1137–1146 (2015). https://doi.org/10.1007/s10545-015-9874-0

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  • DOI: https://doi.org/10.1007/s10545-015-9874-0

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