A Gene Regulatory Program for Meiotic Prophase in the Fetal Ovary

The chromosomal program of meiotic prophase, comprising events such as laying down of meiotic cohesins, synapsis between homologs, and homologous recombination, must be preceded and enabled by the regulated induction of meiotic prophase genes. This gene regulatory program is poorly understood, parti...

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Published in:PLoS genetics 2015-09, Vol.11 (9), p.e1005531-e1005531
Main Authors: Soh, Y Q Shirleen, Junker, Jan Philipp, Gill, Mark E, Mueller, Jacob L, van Oudenaarden, Alexander, Page, David C
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - genetics
Animals
Cell division
Down-Regulation
Female
Gene expression
Gene Expression Regulation, Developmental
Gene Regulatory Networks
Genetic aspects
Genetic regulation
Mammals
Meiosis
Meiotic Prophase I
Observations
Ovaries
Ovary - cytology
Ovary - embryology
Proteins
Scholarships & fellowships
Sheep - embryology
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description The chromosomal program of meiotic prophase, comprising events such as laying down of meiotic cohesins, synapsis between homologs, and homologous recombination, must be preceded and enabled by the regulated induction of meiotic prophase genes. This gene regulatory program is poorly understood, particularly in organisms with a segregated germline. We characterized the gene regulatory program of meiotic prophase as it occurs in the mouse fetal ovary. By profiling gene expression in the mouse fetal ovary in mutants with whole tissue and single-cell techniques, we identified 104 genes expressed specifically in pre-meiotic to pachytene germ cells. We characterized the regulation of these genes by 1) retinoic acid (RA), which induces meiosis, 2) Dazl, which is required for germ cell competence to respond to RA, and 3) Stra8, a downstream target of RA required for the chromosomal program of meiotic prophase. Initial induction of practically all identified meiotic prophase genes requires Dazl. In the presence of Dazl, RA induces at least two pathways: one Stra8-independent, and one Stra8-dependent. Genes vary in their induction by Stra8, spanning fully Stra8-independent, partially Stra8-independent, and fully Stra8-dependent. Thus, Stra8 regulates the entirety of the chromosomal program but plays a more nuanced role in governing the gene expression program. We propose that Stra8-independent gene expression enables the stockpiling of selected meiotic structural proteins prior to the commencement of the chromosomal program. Unexpectedly, we discovered that Stra8 is required for prompt down-regulation of itself and Rec8. Germ cells that have expressed and down-regulated Stra8 are refractory to further Stra8 expression. Negative feedback of Stra8, and subsequent resistance to further Stra8 expression, may ensure a single, restricted pulse of Stra8 expression. Collectively, our findings reveal a gene regulatory logic by which germ cells prepare for the chromosomal program of meiotic prophase, and ensure that it is induced only once.
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Performed the experiments: YQSS JPJ MEG JLM. Analyzed the data: YQSS JPJ MEG JLM. Contributed reagents/materials/analysis tools: YQSS JPJ MEG JLM. Wrote the paper: YQSS DCP.</notes><notes>Current address: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, United States of America</notes><notes>The authors have declared that no competing interests exist.</notes><abstract>The chromosomal program of meiotic prophase, comprising events such as laying down of meiotic cohesins, synapsis between homologs, and homologous recombination, must be preceded and enabled by the regulated induction of meiotic prophase genes. This gene regulatory program is poorly understood, particularly in organisms with a segregated germline. We characterized the gene regulatory program of meiotic prophase as it occurs in the mouse fetal ovary. 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We propose that Stra8-independent gene expression enables the stockpiling of selected meiotic structural proteins prior to the commencement of the chromosomal program. Unexpectedly, we discovered that Stra8 is required for prompt down-regulation of itself and Rec8. Germ cells that have expressed and down-regulated Stra8 are refractory to further Stra8 expression. Negative feedback of Stra8, and subsequent resistance to further Stra8 expression, may ensure a single, restricted pulse of Stra8 expression. Collectively, our findings reveal a gene regulatory logic by which germ cells prepare for the chromosomal program of meiotic prophase, and ensure that it is induced only once.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26378784</pmid><doi>10.1371/journal.pgen.1005531</doi><oa>free_for_read</oa></addata></record>
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subjects Adaptor Proteins, Signal Transducing - genetics
Animals
Cell division
Down-Regulation
Female
Gene expression
Gene Expression Regulation, Developmental
Gene Regulatory Networks
Genetic aspects
Genetic regulation
Mammals
Meiosis
Meiotic Prophase I
Observations
Ovaries
Ovary - cytology
Ovary - embryology
Proteins
Scholarships & fellowships
Sheep - embryology
title A Gene Regulatory Program for Meiotic Prophase in the Fetal Ovary
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