Nanog regulates primordial germ cell migration through Cxcr4b.
Gonadal development in vertebrates depends on the early determination of primordial germ cells (PGCs) and their correct migration to the sites where the gonads develop. Several genes have been implicated in PGC specification and migration in vertebrates. Additionally, some of the genes associated with pluripotency, such as Oct4 and Nanog, are expressed in PGCs and gonads, suggesting a role for these genes in maintaining pluripotency of the germ lineage, which may be considered the only cell type that perpetually maintains stemness properties. Here, we report that medaka Nanog (Ol-Nanog) is expressed in the developing PGCs. Depletion of Ol-Nanog protein causes aberrant migration of PGCs and inhibits expression of Cxcr4b in PGCs, where it normally serves as the receptor of Sdf1a to guide PGC migration. Moreover, chromatin immunoprecipitation analysis demonstrates that Ol-Nanog protein binds to the promoter region of Cxcr4b, suggesting a direct regulation of Cxcr4b by Ol-Nanog. Simultaneous overexpression of Cxcr4b mRNA and depletion of Ol-Nanog protein in PGCs rescues the migration defective phenotype induced by a loss of Ol-Nanog, whereas overexpression of Sdf1a, the ligand for Cxcr4b, does not restore proper PGC migration. These results indicate that Ol-Nanog mediates PGC migration by regulating Cxcr4b expression.
Sánchez-Sánchez
Ana Virginia
AV
Instituto de Investigación Sanitaria, Fundación para la Investigación Hospital La Fe, Valencia, Spain.
Camp
Esther
E
Leal-Tassias
Aránzazu
A
Atkinson
Stuart P
SP
Armstrong
Lyle
L
Díaz-Llopis
Manuel
M
Mullor
José L
JL
D020413:3' Untranslated Regions; D000818:Animals; D001665:Binding Sites; D002465:Cell Movement / Q000235:genetics; D054377:Chemokine CXCL12 / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D005838:Genotype; D005854:Germ Cells / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016366:Open Reading Frames; D009990:Oryzias / Q000196:embryology; D010641:Phenotype; D011401:Promoter Regions, Genetic; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020413:3' Untranslated Regions; D054377:Chemokine CXCL12; D029941:Fish Proteins; D018398:Homeodomain Proteins; D019718:Receptors, CXCR4