Essential Roles of Cyclin Y-Like 1 and Cyclin Y in Dividing Wnt-Responsive Mammary Stem/Progenitor Cells

Cyclin Y family can enhance Wnt/β-catenin signaling in mitosis. Their physiological roles in mammalian development are yet unknown. Here we show that Cyclin Y-like 1 (Ccnyl1) and Cyclin Y (Ccny) have overlapping function and are crucial for mouse embryonic development and mammary stem/progenitor cel...

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Bibliographic Details
Published in:PLoS genetics 2016-05, Vol.12 (5), p.e1006055-e1006055
Main Authors: Zeng, Liyong, Cai, Cheguo, Li, Shan, Wang, Wenjuan, Li, Yaping, Chen, Jiangye, Zhu, Xueliang, Zeng, Yi Arial
Format: Article
Language:English
Subjects:
Animals
beta Catenin - genetics
Biology and Life Sciences
Breasts
Cell cycle
Cell Cycle - genetics
Cell division
Cell Proliferation - genetics
Cyclins - genetics
Embryonic Development - genetics
Experiments
Female
Gene expression
Kinases
Low Density Lipoprotein Receptor-Related Protein-6 - genetics
Mammals
Mammary Glands, Animal - growth & development
Mammary Glands, Animal - metabolism
Medicine and Health Sciences
Mice
Mice, Knockout
Phosphorylation
Physiological aspects
Physiology
Pregnancy
Regeneration - genetics
Research and Analysis Methods
Rodents
Roles
Stem cells
Wnt proteins
Wnt Signaling Pathway - genetics
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Summary:Cyclin Y family can enhance Wnt/β-catenin signaling in mitosis. Their physiological roles in mammalian development are yet unknown. Here we show that Cyclin Y-like 1 (Ccnyl1) and Cyclin Y (Ccny) have overlapping function and are crucial for mouse embryonic development and mammary stem/progenitor cell functions. Double knockout of Ccnys results in embryonic lethality at E16.5. In pubertal development, mammary terminal end buds robustly express Ccnyl1. Depletion of Ccnys leads to reduction of Lrp6 phosphorylation, hampering β-catenin activities and abolishing mammary stem/progenitor cell expansion in vitro. In lineage tracing experiments, Ccnys-deficient mammary cells lose their competitiveness and cease to contribute to mammary development. In transplantation assays, Ccnys-deficient mammary cells fail to reconstitute, whereas constitutively active β-catenin restores their regeneration abilities. Together, our results demonstrate the physiological significance of Ccnys-mediated mitotic Wnt signaling in embryonic development and mammary stem/progenitor cells, and reveal insights in the molecular mechanisms orchestrating cell cycle progression and maintenance of stem cell properties.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1006055