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Updated: Mar 23, 2026

Loss- and Gain-of-function Approach to Investigate Early Cell Fate Determinants in Preimplantation Mouse Embryos
Published on: June 6, 2016
Loss of MAX results in meiotic entry in mouse embryonic and germline stem cells
Ayumu Suzuki1, Masataka Hirasaki1, Tomoaki Hishida1,2
1Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical University, Yamane Hidaka, Saitama 350-1241, Japan.
Abstract:
Meiosis is a unique process that allows the generation of reproductive cells. It remains largely unknown how meiosis is initiated in germ cells and why non-germline cells do not undergo meiosis. We previously demonstrated that knockdown of Max expression, a gene encoding a partner of MYC family proteins, strongly activates expression of germ cell-related genes in ESCs. Here we find that complete ablation of Max expression in ESCs results in profound cytological changes reminiscent of cells undergoing meiotic cell division. Furthermore, our analyses uncovers that Max expression is transiently attenuated in germ cells undergoing meiosis in vivo and its forced reduction induces meiosis-like cytological changes in cultured germline stem cells. Mechanistically, Max depletion alterations are, in part, due to impairment of the function of an atypical PRC1 complex (PRC1.6), in which MAX is one of the components. Our data highlight MAX as a new regulator of meiotic onset.
Insights
Max protein regulates the initiation of meiosis, a crucial process for reproductive cell generation. Its depletion in stem cells triggers meiosis-like changes, revealing its role in germ cell development.
Area of Science:
- Cell Biology
- Developmental Biology
- Genetics
Background:
- Meiosis is essential for sexual reproduction, but its initiation mechanisms remain unclear.
- Understanding why only germ cells undergo meiosis is a key question in developmental biology.
- Previous studies indicated Max protein's role in regulating germ cell-related gene expression.
Purpose of the Study:
- To investigate the role of Max protein in the initiation of meiosis.
- To determine if Max protein regulates meiotic processes in germ cells and non-germline cells.
- To elucidate the molecular mechanisms by which Max influences meiotic onset.
Main Methods:
- Studied Max expression in embryonic stem cells (ESCs) and germ cells.
- Utilized gene knockdown and ablation techniques to alter Max expression.
- Performed cytological analyses to observe cellular changes.
- Investigated the interaction of Max with the PRC1.6 complex.
Main Results:
- Complete Max ablation in ESCs induced meiotic-like cytological changes.
- Max expression was transiently reduced in germ cells during meiosis in vivo.
- Forced reduction of Max in cultured germline stem cells also induced meiosis-like changes.
- Max depletion impaired the function of the PRC1.6 complex.
Conclusions:
- Max protein is a novel regulator of meiotic onset.
- Max plays a critical role in controlling the initiation of meiosis in germ cells.
- Dysregulation of Max impacts meiotic processes through pathways involving the PRC1.6 complex.
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