DISSECTING THE ROLE OF SIALOGLYCANS IN EMBRYONIC DEVELOPMENT

• Applicant: Dr. Birgit Weinhold
• Subject Area: Cell Biology
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 409784463

The negatively charged sugar sialic acid (Sia) occupies the outermost position in the bulk of cell surface glycans. Lack of sialylated glycans due to genetic ablation of the Sia-activating enzyme CMP-sialic acid synthase (CMAS) resulted in embryonic lethality around embryonic day 9.5 (E9.5) in mice. We showed that Sia is dispensable for early development of the embryo proper but pivotal for fetal-maternal immune homeostasis during pregnancy, i.e., for protecting the allograft implant against attack by the maternal innate immune system. Sialylation-deficiency resulted in impaired control of the complement pathway with its key complement component 3 (C3), causing tissue inflammation, destruction, and embryonic lethality. The Cmas model will allow defining the exact molecular mechanisms by which Sia impacts the complement system at the fetal-maternal interface. To overcome C3-mediated embryonic lethality and to uncover Sia functions apart from complement regulation we aim to combine the Cmas knockout with a C3 knockout mouse.

• DFG Programme: Research Units
• Subproject of: FOR 2953: Sialic Acid as Regulator in Development and Immunity