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Published on: February 6, 2018
Germ cell differentiation and synaptonemal complex formation are disrupted in CPEB knockout mice
1Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester 01655, USA.
Abstract:
CPEB is a sequence-specific RNA binding protein that regulates translation during vertebrate oocyte maturation. Adult female CPEB knockout mice contained vestigial ovaries that were devoid of oocytes; ovaries from mid-gestation embryos contained oocytes that were arrested at the pachytene stage. Male CPEB null mice also contained germ cells arrested at pachytene. The germ cells from the knockout mice harbored fragmented chromatin, suggesting a possible defect in homologous chromosome adhesion or synapsis. Two CPE-containing synaptonemal complex protein mRNAs, which interact with CPEB in vitro and in vivo, contained shortened poly(A) tails and mostly failed to sediment with polysomes in the null mice. Synaptonemal complexes were not detected in these animals. CPEB therefore controls germ cell differentiation by regulating the formation of the synaptonemal complex.
Insights
Cytoplasmic polyadenylation element-binding protein (CPEB) is essential for vertebrate germ cell development. Loss of CPEB function in mice leads to arrested germ cell development and failed synaptonemal complex formation.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Cytoplasmic polyadenylation element-binding protein (CPEB) is a key regulator of translation during oocyte maturation.
- CPEB's role in germ cell development and meiosis is not fully understood.
Purpose of the Study:
- To investigate the function of CPEB in vertebrate germ cell development and meiosis.
- To determine the molecular mechanisms by which CPEB controls germ cell differentiation.
Main Methods:
- Generation and analysis of CPEB knockout mice.
- Examination of germ cell morphology and chromatin structure.
- Analysis of synaptonemal complex protein mRNA levels and polysome association.
Main Results:
- CPEB knockout mice exhibited vestigial ovaries and arrested oocytes at the pachytene stage.
- Male CPEB null mice also showed pachytene-arrested germ cells with fragmented chromatin.
- Two synaptonemal complex protein mRNAs were downregulated and failed to associate with polysomes in CPEB null mice.
- Synaptonemal complexes were absent in CPEB knockout mice.
Conclusions:
- CPEB is crucial for vertebrate germ cell differentiation and progression through meiosis.
- CPEB regulates the formation of the synaptonemal complex, essential for homologous chromosome pairing and segregation.
- CPEB controls germ cell development by modulating the translation of key meiotic proteins.
