title: Discrete somatic niches coordinate proliferation and migration of primordial germ cells via Wnt signaling.
abstract: Inheritance depends on the expansion of a small number of primordial germ cells (PGCs) in the early embryo. Proliferation of mammalian PGCs is concurrent with their movement through changing microenvironments; however, mechanisms coordinating these conflicting processes remain unclear. Here, we find that PGC proliferation varies by location rather than embryonic age. Ror2 and Wnt5a mutants with mislocalized PGCs corroborate the microenvironmental regulation of the cell cycle, except in the hindgut, where Wnt5a is highly expressed. Molecular and genetic evidence suggests that Wnt5a acts via Ror2 to suppress β-catenin-dependent Wnt signaling in PGCs and limit their proliferation in specific locations, which we validate by overactivating β-catenin in PGCs. Our results suggest that the balance between expansion and movement of migratory PGCs is fine-tuned in different niches by the opposing β-catenin-dependent and Ror2-mediated pathways through Wnt5a This could serve as a selective mechanism to favor early and efficient migrators with clonal dominance in the ensuing germ cell pool while penalizing stragglers.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Reproductive Sciences, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94043.
authors.forename: Andrea V
authors.initials: AV
authors.lastname: Cantú
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Reproductive Sciences, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94043.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Altshuler-Keylin
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Reproductive Sciences, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94043 diana.laird@ucsf.edu.
authors.forename: Diana J
authors.identifier: 0000-0002-4930-0560
authors.initials: DJ
authors.lastname: Laird
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D004064:Digestive System / Q000166:cytology; D005260:Female; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000378:metabolism; D060449:Wnt Signaling Pathway; D000071818:Wnt-5a Protein / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000071818:Wnt-5a Protein; D051176:beta Catenin; D049452:Green Fluorescent Proteins; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; C477010:Ror2 protein, mouse