title: Meiotic onset is reliant on spatial distribution but independent of germ cell number in the mouse ovary.
abstract: Mouse ovarian germ cells enter meiosis in a wave that propagates from anterior to posterior, but little is known about contribution of germ cells to initiation or propagation of meiosis. In a Ror2 mutant with diminished germ cell number and migration, we find that overall timing of meiotic initiation is delayed at the population level. We use chemotherapeutic depletion to exclude a profoundly reduced number of germ cells as a cause for meiotic delay. We rule out sex reversal or failure to specify somatic support cells as contributors to the meiotic phenotype. Instead, we find that anomalies in the distribution of germ cells as well as gonad shape in mutants contribute to aberrant initiation of meiosis. Our analysis supports a model of meiotic initiation via diffusible signal(s), excludes a role for germ cells in commencing the meiotic wave and furnishes the first phenotypic demonstration of the wave of meiotic entry. Finally, our studies underscore the importance of considering germ cell migration defects while studying meiosis to discern secondary effects resulting from positioning versus primary meiotic entry phenotypes.
authors.affiliation: Department of Ob/Gyn and Reproductive Sciences, Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA.
authors.forename: Ripla
authors.initials: R
authors.lastname: Arora
authors.affiliation: University Paris Diderot, Sorbonne Paris Cite, Laboratory of Development of the Gonads; CEA, DSV, iRCM, SCSR, LDG; INSERM, Unit of Genetic Stability, Stem cells and Radiation, UMR-967; University Paris-Sud, Fontenay-aux-Roses F-92265, France.
authors.forename: Emilie
authors.identifier: 0000-0003-0284-4760
authors.initials: E
authors.lastname: Abby
authors.affiliation: Department of Ob/Gyn and Reproductive Sciences, Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA.
authors.forename: Adam D J
authors.initials: AD
authors.lastname: Ross
authors.affiliation: Department of Ob/Gyn and Reproductive Sciences, Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA.
authors.forename: Andrea V
authors.initials: AV
authors.lastname: Cantu
authors.affiliation: Department of Ob/Gyn and Reproductive Sciences, Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA.
authors.forename: Michael D
authors.identifier: 0000-0001-7603-2402
authors.initials: MD
authors.lastname: Kissner
authors.affiliation: Department of Ob/Gyn and Reproductive Sciences, Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA.
authors.forename: Vianca
authors.initials: V
authors.lastname: Castro
authors.affiliation: Department of Cell Biology and Human Anatomy, University of California, Davis School of Medicine, 4422 Tupper Hall, Davis, CA 95616, USA.
authors.forename: Hsin-Yi Henry
authors.initials: HY
authors.lastname: Ho
authors.affiliation: University Paris Diderot, Sorbonne Paris Cite, Laboratory of Development of the Gonads; CEA, DSV, iRCM, SCSR, LDG; INSERM, Unit of Genetic Stability, Stem cells and Radiation, UMR-967; University Paris-Sud, Fontenay-aux-Roses F-92265, France.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Livera
authors.affiliation: Department of Ob/Gyn and Reproductive Sciences, Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA diana.laird@ucsf.edu.
authors.forename: Diana J
authors.identifier: 0000-0002-4930-0560
authors.initials: DJ
authors.lastname: Laird
mesh_terms: D000818:Animals; D002452:Cell Count; D002465:Cell Movement / Q000235:genetics; D048430:Cell Shape / Q000235:genetics; D005260:Female; D005854:Germ Cells / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D006066:Gonads / Q000254:growth & development / Q000473:pathology*; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D009154:Mutation; D010053:Ovary / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D057050:Receptor Tyrosine Kinase-like Orphan Receptors; C477010:Ror2 protein, mouse
keywords: Germ cell; Gonad; Meiosis; Migration; Ror2; Wave