Rolle der Sialoglykane für die Embryonalentwicklung

• Antragstellerin: Dr. Birgit Weinhold
• Fachliche Zuordnung: Zellbiologie
• Förderung: Förderung von 2019 bis 2023
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 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-Verfahren: Forschungsgruppen
• Teilprojekt zu: FOR 2953: Sialinsäure als Regulator in Entwicklung und Immunität