title: The chemokine SDF1/CXCL12 and its receptor CXCR4 regulate mouse germ cell migration and survival.
abstract: In mouse embryos, germ cells arise during gastrulation and migrate to the early gonad. First, they emerge from the primitive streak into the region of the endoderm that forms the hindgut. Later in development, a second phase of migration takes place in which they migrate out of the gut to the genital ridges. There, they co-assemble with somatic cells to form the gonad. In vitro studies in the mouse, and genetic studies in other organisms, suggest that at least part of this process is in response to secreted signals from other tissues. Recent genetic evidence in zebrafish has shown that the interaction between stromal cell-derived factor 1 (SDF1) and its G-protein-coupled receptor CXCR4, already known to control many types of normal and pathological cell migrations, is also required for the normal migration of primordial germ cells. We show that in the mouse, germ cell migration and survival requires the SDF1/CXCR4 interaction. First, migrating germ cells express CXCR4, whilst the body wall mesenchyme and genital ridges express the ligand SDF1. Second, the addition of exogenous SDF1 to living embryo cultures causes aberrant germ cell migration from the gut. Third, germ cells in embryos carrying targeted mutations in CXCR4 do not colonize the gonad normally. However, at earlier stages in the hindgut, germ cells are unaffected in CXCR4(-/-) embryos. Germ cell counts at different stages suggest that SDF1/CXCR4 interaction also mediates germ cell survival. These results show that the SDF1/CXCR4 interaction is specifically required for the colonization of the gonads by primordial germ cells, but not for earlier stages in germ cell migration. This demonstrates a high degree of evolutionary conservation of part of the mechanism, but also an area of evolutionary divergence.
authors.affiliation: Division of Developmental Biology, Children's Hospital Research Foundation, Cincinnati, OH 45229, USA.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Molyneaux
authors.forename: Hélène
authors.initials: H
authors.lastname: Zinszner
authors.forename: Prabhat S
authors.initials: PS
authors.lastname: Kunwar
authors.forename: Kyle
authors.initials: K
authors.lastname: Schaible
authors.forename: Jürg
authors.initials: J
authors.lastname: Stebler
authors.forename: Mary Jean
authors.initials: MJ
authors.lastname: Sunshine
authors.forename: William
authors.initials: W
authors.lastname: O'Brien
authors.forename: Erez
authors.initials: E
authors.lastname: Raz
authors.forename: Dan
authors.initials: D
authors.lastname: Littman
authors.forename: Chris
authors.initials: C
authors.lastname: Wylie
authors.forename: Ruth
authors.initials: R
authors.lastname: Lehmann
mesh_terms: D000818:Animals; D019521:Body Patterning; D002465:Cell Movement / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D004625:Embryo, Nonmammalian; D005854:Germ Cells / Q000166:cytology / Q000502:physiology*; D006066:Gonads / Q000254:growth & development; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes; D015027:Zebrafish
chemical_list: D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4