Meiosis is the process of producing haploid gametes through a series of complex chromosomal events and the coordinated action of various proteins.The mitochondrial protease complex(ClpXP),which consists of caseinolyti...Meiosis is the process of producing haploid gametes through a series of complex chromosomal events and the coordinated action of various proteins.The mitochondrial protease complex(ClpXP),which consists of caseinolytic mitochondrial matrix peptidase X(ClpX)and caseinolytic protease P(ClpP)and mediates the degradation of misfolded,damaged,and oxidized proteins,is essential for maintaining mitochondrial homeostasis.ClpXP has been implicated in meiosis regulation,but its precise role is currently unknown.In this study,we engineered an inducible male germ cell-specific knockout caseinolytic mitochondrial matrix peptidase X(Clpx^(cKO))mouse model to investigate the function of ClpX in meiosis.We found that disrupting Clpx in male mice induced germ cell apoptosis and led to an absence of sperm in the epididymis.Specifically,it caused asynapsis of homologous chromosomes and impaired meiotic recombination,resulting in meiotic arrest in the zygotene-to-pachytene transition phase.The loss of ClpX compromised the double-strand break(DSB)repair machinery by markedly reducing the recruitment of DNA repair protein RAD51 homolog 1(RAD51)to DSB sites.This dysfunction may be due to an insufficient supply of energy from the aberrant mitochondria in Clpx^(cKO) spermatocytes,as discerned by electron microscopy.Furthermore,ubiquitination signals on chromosomes and the expression of oxidative phosphorylation subunits were both significantly attenuated in Clpx^(cKO) spermatocytes.Taken together,we propose that ClpX is essential for maintaining mitochondrial protein homeostasis and ensuring homologous chromosome pairing,synapsis,and recombination in spermatocytes during meiotic prophase I.展开更多
Alzheimer’s disease (AD) is characterized by a decline of cognitive functions. Distinctive histopathological hallmarks are neuritic plaques, neurofibrillary tangles, and synaptic alterations. Abnormally enlarged syna...Alzheimer’s disease (AD) is characterized by a decline of cognitive functions. Distinctive histopathological hallmarks are neuritic plaques, neurofibrillary tangles, and synaptic alterations. Abnormally enlarged synaptic structures called “Meganeurite clusters” have been linked to plasticity changes. The aims of this study were to determine if cognitive impairment was related to specific neuritic and synaptic degeneration processes in patients with AD, and if the results of a cognitive test could be correlated with the histopathological damage. The neuropsychological evaluation obtained by the Protocole d’evaluation neuropsychologique optimal (PENO) test battery was used in live AD and control individuals. The histopathological evaluation of their brain after their death was carried out with specific polyclonal and monoclonal antibodies to Aβ, pTau protein, synaptophysin, and GAP-43. Images were obtained by confocal microscopy. The results showed a significant difference between healthy controls and Alzheimer’s patients in neuropsychological evaluation and histopathological hallmarks expression. The most significant positive correlation in AD patients was between memory and language results with the PENO test and the presence of Aβ +pTau+ plaques in the hippocampus. An interesting negative correlation was between cognitive impairment and the presence of Meganeuritic clusters, considered as “plasticity” markers. These results strongly supported the use of the PENO battery test to evaluate the progression of cognitive impairment in AD prone individuals and patients due to the strong correlation of the test results with histopathological brain lesions characteristic of Alzheimer’s disease.展开更多
Meiosis is the crucial process by which sexually propagating eukaryotes give rise to haploid gametes from diploid cells. Several key processes, like homologous chromosomes pairing, synapsis, recombination, and segrega...Meiosis is the crucial process by which sexually propagating eukaryotes give rise to haploid gametes from diploid cells. Several key processes, like homologous chromosomes pairing, synapsis, recombination, and segregation, sequentially take place in meiosis. Although these widely conserved events are under both genetic and epigenetic control, the accurate details of molecular mechanisms are continuing to investigate. Rice is a good model organism for exploring the molecular mechanisms of meiosis in higher plants. So far, 28 rice meiotic genes have been characterized. In this review, we give an overview of the discovery of rice meiotic genes in the last ten years, with a particular focus on their functions in meiosis.展开更多
The synaptonemal complex(SC)is a meiosis-specific proteinaceous macromolecular structure that assembles between paired homologous chromosomes during meiosis in various eukaryotes.The SC has a highly conserved ultrastr...The synaptonemal complex(SC)is a meiosis-specific proteinaceous macromolecular structure that assembles between paired homologous chromosomes during meiosis in various eukaryotes.The SC has a highly conserved ultrastructure and plays critical roles in controlling multiple steps in meiotic recombination and crossover formation,ensuring accurate meiotic chromosome segregation.Recent studies in different organisms,facilitated by advances in super-resolution microscopy,have provided insights into the macromolecular structure of the SC,including the internal organization of the meiotic chromosome axis and SC central region,the regulatory pathways that control SC assembly and dynamics,and the biological functions exerted by the SC and its substructures.This review summarizes recent discoveries about how the SC is organized and regulated that help to explain the biological functions associated with this meiosis-specific structure.展开更多
a-kleisins are core components of meiotic and mitotic cohesin complexes. Arabidopsis contains genes encoding four a-kleisins. SYN1, a REC8 ortholog, is essential for meiosis, while SYN2 and SYN4 appear to be SCCI orth...a-kleisins are core components of meiotic and mitotic cohesin complexes. Arabidopsis contains genes encoding four a-kleisins. SYN1, a REC8 ortholog, is essential for meiosis, while SYN2 and SYN4 appear to be SCCI orthologs and function in mitosis. SYN3 is enriched in the nucleolus of meiotic and mitotic cells and is essential for megagametogenesis. It was recently shown that expression of SYN3-RNAi constructs in buds cause changes in meiotic gene expression that result in meiotic alterations. In this report we show that expression of SYN3 from the 35S promoter with either a c-terminal Myc or FAST tag causes a reduction in SYN1 mRNA levels that results in al- terations in sister chromatid cohesion, homologous chromosome synapsis female meiosis. and synaptonemal complex formation during both male and展开更多
Spermatogenesis is a highly complex developmental process that typically consists of mitosis, meiosis, and spermiogenesis. DNA/RNA helicase DHX36, a unique guanine-quadruplex (G4) resolvase, plays crucial roles in a v...Spermatogenesis is a highly complex developmental process that typically consists of mitosis, meiosis, and spermiogenesis. DNA/RNA helicase DHX36, a unique guanine-quadruplex (G4) resolvase, plays crucial roles in a variety of biological processes. We previously showed that DHX36 is highly expressed in male germ cells with the highest level in zygotene spermatocytes. Here, we deleted Dhx36 in advanced germ cells with Stra8-GFPCre and found that a Dhx36 deficiency in the differentiated spermatogonia leads to meiotic defects and abnormal spermiogenesis. These defects in late stages of spermatogenesis arise from dysregulated transcription of G4-harboring genes, which are required for meiosis. Thus, this study reveals that Dhx36 plays crucial roles in late stages of spermatogenesis.展开更多
基金supported by the Shenzhen Science and Technology Program,China(No.KQTD20190929172749226).
文摘Meiosis is the process of producing haploid gametes through a series of complex chromosomal events and the coordinated action of various proteins.The mitochondrial protease complex(ClpXP),which consists of caseinolytic mitochondrial matrix peptidase X(ClpX)and caseinolytic protease P(ClpP)and mediates the degradation of misfolded,damaged,and oxidized proteins,is essential for maintaining mitochondrial homeostasis.ClpXP has been implicated in meiosis regulation,but its precise role is currently unknown.In this study,we engineered an inducible male germ cell-specific knockout caseinolytic mitochondrial matrix peptidase X(Clpx^(cKO))mouse model to investigate the function of ClpX in meiosis.We found that disrupting Clpx in male mice induced germ cell apoptosis and led to an absence of sperm in the epididymis.Specifically,it caused asynapsis of homologous chromosomes and impaired meiotic recombination,resulting in meiotic arrest in the zygotene-to-pachytene transition phase.The loss of ClpX compromised the double-strand break(DSB)repair machinery by markedly reducing the recruitment of DNA repair protein RAD51 homolog 1(RAD51)to DSB sites.This dysfunction may be due to an insufficient supply of energy from the aberrant mitochondria in Clpx^(cKO) spermatocytes,as discerned by electron microscopy.Furthermore,ubiquitination signals on chromosomes and the expression of oxidative phosphorylation subunits were both significantly attenuated in Clpx^(cKO) spermatocytes.Taken together,we propose that ClpX is essential for maintaining mitochondrial protein homeostasis and ensuring homologous chromosome pairing,synapsis,and recombination in spermatocytes during meiotic prophase I.
文摘Alzheimer’s disease (AD) is characterized by a decline of cognitive functions. Distinctive histopathological hallmarks are neuritic plaques, neurofibrillary tangles, and synaptic alterations. Abnormally enlarged synaptic structures called “Meganeurite clusters” have been linked to plasticity changes. The aims of this study were to determine if cognitive impairment was related to specific neuritic and synaptic degeneration processes in patients with AD, and if the results of a cognitive test could be correlated with the histopathological damage. The neuropsychological evaluation obtained by the Protocole d’evaluation neuropsychologique optimal (PENO) test battery was used in live AD and control individuals. The histopathological evaluation of their brain after their death was carried out with specific polyclonal and monoclonal antibodies to Aβ, pTau protein, synaptophysin, and GAP-43. Images were obtained by confocal microscopy. The results showed a significant difference between healthy controls and Alzheimer’s patients in neuropsychological evaluation and histopathological hallmarks expression. The most significant positive correlation in AD patients was between memory and language results with the PENO test and the presence of Aβ +pTau+ plaques in the hippocampus. An interesting negative correlation was between cognitive impairment and the presence of Meganeuritic clusters, considered as “plasticity” markers. These results strongly supported the use of the PENO battery test to evaluate the progression of cognitive impairment in AD prone individuals and patients due to the strong correlation of the test results with histopathological brain lesions characteristic of Alzheimer’s disease.
基金supported by grants from the National Natural Science Foundation of China(Nos.31360260, 31230038 and U1302261)
文摘Meiosis is the crucial process by which sexually propagating eukaryotes give rise to haploid gametes from diploid cells. Several key processes, like homologous chromosomes pairing, synapsis, recombination, and segregation, sequentially take place in meiosis. Although these widely conserved events are under both genetic and epigenetic control, the accurate details of molecular mechanisms are continuing to investigate. Rice is a good model organism for exploring the molecular mechanisms of meiosis in higher plants. So far, 28 rice meiotic genes have been characterized. In this review, we give an overview of the discovery of rice meiotic genes in the last ten years, with a particular focus on their functions in meiosis.
基金This work was supported by grants from the National Natural Science Foundation of China(No.31871360,No.32022018,and No.31701176 to JMG)。
文摘The synaptonemal complex(SC)is a meiosis-specific proteinaceous macromolecular structure that assembles between paired homologous chromosomes during meiosis in various eukaryotes.The SC has a highly conserved ultrastructure and plays critical roles in controlling multiple steps in meiotic recombination and crossover formation,ensuring accurate meiotic chromosome segregation.Recent studies in different organisms,facilitated by advances in super-resolution microscopy,have provided insights into the macromolecular structure of the SC,including the internal organization of the meiotic chromosome axis and SC central region,the regulatory pathways that control SC assembly and dynamics,and the biological functions exerted by the SC and its substructures.This review summarizes recent discoveries about how the SC is organized and regulated that help to explain the biological functions associated with this meiosis-specific structure.
基金supported by a grant from the National Science Foundation of USA(No.MCB0718191)
文摘a-kleisins are core components of meiotic and mitotic cohesin complexes. Arabidopsis contains genes encoding four a-kleisins. SYN1, a REC8 ortholog, is essential for meiosis, while SYN2 and SYN4 appear to be SCCI orthologs and function in mitosis. SYN3 is enriched in the nucleolus of meiotic and mitotic cells and is essential for megagametogenesis. It was recently shown that expression of SYN3-RNAi constructs in buds cause changes in meiotic gene expression that result in meiotic alterations. In this report we show that expression of SYN3 from the 35S promoter with either a c-terminal Myc or FAST tag causes a reduction in SYN1 mRNA levels that results in al- terations in sister chromatid cohesion, homologous chromosome synapsis female meiosis. and synaptonemal complex formation during both male and
基金supported by grants from the National Key R&D Program of China(2021YFC2700200 and 2022YFC2702602)the National Natural Science Foundation of China(31930034)the Science and Technology Commission of Shanghai Municipality(19JC1415800 to M.-H.T.).
文摘Spermatogenesis is a highly complex developmental process that typically consists of mitosis, meiosis, and spermiogenesis. DNA/RNA helicase DHX36, a unique guanine-quadruplex (G4) resolvase, plays crucial roles in a variety of biological processes. We previously showed that DHX36 is highly expressed in male germ cells with the highest level in zygotene spermatocytes. Here, we deleted Dhx36 in advanced germ cells with Stra8-GFPCre and found that a Dhx36 deficiency in the differentiated spermatogonia leads to meiotic defects and abnormal spermiogenesis. These defects in late stages of spermatogenesis arise from dysregulated transcription of G4-harboring genes, which are required for meiosis. Thus, this study reveals that Dhx36 plays crucial roles in late stages of spermatogenesis.
