14 research outputs found
A Mammal-Specific Doublesex Homolog Associates with Male Sex Chromatin and Is Required for Male Meiosis
Gametogenesis is a sexually dimorphic process requiring profound differences in germ cell differentiation between the sexes. In mammals, the presence of heteromorphic sex chromosomes in males creates additional sex-specific challenges, including incomplete X and Y pairing during meiotic prophase. This triggers formation of a heterochromatin domain, the XY body. The XY body disassembles after prophase, but specialized sex chromatin persists, with further modification, through meiosis. Here, we investigate the function of DMRT7, a mammal-specific protein related to the invertebrate sexual regulators Doublesex and MAB-3. We find that DMRT7 preferentially localizes to the XY body in the pachytene stage of meiotic prophase and is required for male meiosis. In Dmrt7 mutants, meiotic pairing and recombination appear normal, and a transcriptionally silenced XY body with appropriate chromatin marks is formed, but most germ cells undergo apoptosis during pachynema. A minority of mutant cells can progress to diplonema, but many of these escaping cells have abnormal sex chromatin lacking histone H3K9 di- and trimethylation and heterochromatin protein 1Ī² accumulation, modifications that normally occur between pachynema and diplonema. Based on the localization of DMRT7 to the XY body and the sex chromatin defects observed in Dmrt7 mutants, we conclude that DMRT7 plays a role in the sex chromatin transformation that occurs between pachynema and diplonema. We suggest that DMRT7 may help control the transition from meiotic sex chromosome inactivation to postmeiotic sex chromatin in males. In addition, because it is found in all branches of mammals, but not in other vertebrates, Dmrt7 may shed light on evolution of meiosis and of sex chromatin
Mutation in Mouse Hei10, an E3 Ubiquitin Ligase, Disrupts Meiotic Crossing Over
Crossing over during meiotic prophase I is required for sexual reproduction in mice and contributes to genome-wide genetic diversity. Here we report on the characterization of an N-ethyl-N-nitrosourea-induced, recessive allele called mei4, which causes sterility in both sexes owing to meiotic defects. In mutant spermatocytes, chromosomes fail to congress properly at the metaphase plate, leading to arrest and apoptosis before the first meiotic division. Mutant oocytes have a similar chromosomal phenotype but in vitro can undergo meiotic divisions and fertilization before arresting. During late meiotic prophase in mei4 mutant males, absence of cyclin dependent kinase 2 and mismatch repair protein association from chromosome cores is correlated with the premature separation of bivalents at diplonema owing to lack of chiasmata. We have identified the causative mutation, a transversion in the 5ā² splice donor site of exon 1 in the mouse ortholog of Human Enhancer of Invasion 10 (Hei10; also known as Gm288 in mouse and CCNB1IP1 in human), a putative B-type cyclin E3 ubiquitin ligase. Importantly, orthologs of Hei10 are found exclusively in deuterostomes and not in more ancestral protostomes such as yeast, worms, or flies. The cloning and characterization of the mei4 allele of Hei10 demonstrates a novel link between cell cycle regulation and mismatch repair during prophase I
SDF-1 Acutely Promotes the Physical Association of Megakaryocytes with Vascular Endothelium in the Bone Marrow and Increases the Number of Circulating Platelets.
End-of-Life Care for Children Enrolled in a Community-Based Pediatric Palliative Care Program
Racial and seasonal differences in 25-hydroxyvitamin D detected in maternal sera frozen for over 40 years
Abnormal Sex Chromatin in Cells Staged by Chromosome Pairing Status
<div><p>(A) Spread of wild-type germ cell stained with DAPI, anti-SYCP3, and anti-HP1Ī² showing chromosome morphology typical of diplonema and internalized XY body with HP1Ī² accumulation.</p><p>(B) Spread of <i>Dmrt7</i> mutant germ cell showing normal diplotene chromosome morphology and internalized XY body, but no HP1Ī² accumulation in the XY body.</p><p>XY chromosome pairs are indicated by arrow.</p></div
GPCR/EGFR Cross Talk Is Conserved in Gonadal and Adrenal Steroidogenesis but Is Uniquely Regulated by Matrix Metalloproteinases 2 and 9 in the Ovary
Steroidogenesis in all major tissues requires cross-talk between GPRC and EGFR receptors. In the ovary, this cross-talk is uniquely mediated by MMPs 2 and 9