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GPI transamidase complex is required for primordial germ cell migration and development in zebrafish
Weiying Zhang1,† , Yaqi Li1,† , Jing Chen2 , Likun Yao1 , Bingjie Zhang3 , Lin Zhang4 , Boqi Liu5 , Weimin Shen1 , Anming Meng1,6 , Xiaotong Wu1,*
1Laboratory of Molecular Developmental Biology, State Key Laboratory of Membrane Biology, Tsinghua–Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
2China West China Hospital, Sichuan University, Chengdu 610044, China
3Tsinghua–Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
4State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Science, Beijing 100101, China
5State Key Laboratory of Membrane Biology, Tsinghua University–Peking University Joint Center for Life Sciences, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University, Beijing 100084, China
6Guangzhou Laboratory, Guangzhou 510320, China
These authors contributed equally to this work
*Correspondence to:Xiaotong Wu , Email:wuxt@mail.tsinghua.edu.cn
J Mol Cell Biol, Volume 16, Issue 12, December 2024, mjae058,  https://doi.org/10.1093/jmcb/mjae058
Keyword: GPI transamidase complex, Pigu, primordial germ cell, cell migration, zebrafish

Proteins without transmembrane domains could be anchored to the cell surface for regulating various biological processes when covalently linked to glycosylphosphatidylinositol (GPI) molecules by the GPI transamidase (GPIT) complex. However, it remains poorly understood whether and how the GPIT complex affects primordial germ cell (PGC) development. In this study, we report the important roles of the GPIT complex in PGC migration and development in zebrafish embryos. Mutation of pigu or pigk, both encoding essential GPIT complex subunits, resulted in defective PGC migration with ectopically located PGCs and reduction of PGC counts. Notably, a detailed analysis of filopodia in PGCs revealed the attenuated polarity of filopodia distribution along the migration direction in mutant embryos. PGC transplantation and PGC-specific rescue experiments demonstrated that both PGC and somatic cell-expressed Pigu are required for PGC migration. Furthermore, expression levels of PGC-specific genes decreased in pigu mutant PGCs with the derepression of somatic cell genes. Hence, we propose that the GPIT complex plays a critical role during PGC migration and development.