title: Msx1 and Msx2 function together in the regulation of primordial germ cell migration in the mouse.
abstract: Primordial germ cells (PGCs) are a highly migratory cell population that gives rise to eggs and sperm. Much is known about PGC specification, but less about the processes that control PGC migration. In this study, we document a deficiency in PGC development in embryos carrying global homozygous null mutations in Msx1 and Msx2, both immediate downstream effectors of Bmp signaling pathway. We show that Msx1(-/-);Msx2(-/-) mutant embryos have defects in PGC migration as well as a reduced number of PGCs. These phenotypes are also evident in a Mesp1-Cre-mediated mesoderm-specific mutant line of Msx1 and Msx2. Since PGCs are not marked in Mesp1-lineage tracing, our results suggest that Msx1 and Msx2 function cell non-autonomously in directing PGC migration. Consistent with this hypothesis, we noted an upregulation of fibronectin, well known as a mediator of cell migration, in tissues through which PGCs migrate. We also noted a reduction in the expression of Wnt5a and an increase in the expression in Bmp4 in such tissues in Msx1(-/-);Msx2(-/-) mutants, both known effectors of PGC development.
authors.affiliation: Department of Biochemistry and Molecular Biology, Norris Cancer Hospital, University of Southern California, Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90089-9176, USA.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Molecular Biology, Norris Cancer Hospital, University of Southern California, Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90089-9176, USA.
authors.forename: Man-Chun
authors.initials: MC
authors.lastname: Ting
authors.affiliation: Department of Biochemistry and Molecular Biology, Norris Cancer Hospital, University of Southern California, Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90089-9176, USA.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ishii
authors.affiliation: Department of Biochemistry and Molecular Biology, Norris Cancer Hospital, University of Southern California, Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90089-9176, USA. Electronic address: maxson@usc.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Maxson
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000096:biosynthesis; D002465:Cell Movement / Q000235:genetics*; D000066473:Embryonic Germ Cells / Q000166:cytology* / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D051957:MSX1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D000071818:Wnt-5a Protein / Q000096:biosynthesis
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D055415:Bone Morphogenetic Protein 4; D005353:Fibronectins; D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; D000071818:Wnt-5a Protein; C525810:Bmp4 protein, mouse; C084119:MSX2 protein; C101538:Mesp1 protein, mouse; C484084:Msx1 protein, mouse; C438615:Wnt5a protein, mouse
keywords: Bmp pathway; Fibronectin; Msx1, Msx2; PGC; PGC migration; Primordial germ cell; Wnt5a