Nanog Regulates Primordial Germ Cell Migration Through Cxcr4b

6533b82efe1ef96bd1293f00

RESEARCH PRODUCT

Nanog Regulates Primordial Germ Cell Migration Through Cxcr4b

Manuel Díaz-llopis Aránzazu Leal-tassias Ana V. Sánchez-sánchez Lyle Armstrong José L. Mullor Stuart P. Atkinson Esther Camp

subject

Fish Proteins Homeobox protein NANOG Chromatin Immunoprecipitation Receptors CXCR4 endocrine system Cell type Genotype Oryzias Biology Nanog Cxcr4b Open Reading Frames Cell Movement Animals Promoter Regions Genetic 3' Untranslated Regions Gene In Situ Hybridization reproductive and urinary physiology Homeodomain Proteins Regulation of gene expression Messenger RNA Binding Sites Reverse Transcriptase Polymerase Chain Reaction urogenital system Three prime untranslated region PGC Gene Expression Regulation Developmental Cell Biology Immunohistochemistry Phenotype Molecular biology Chemokine CXCL12 Medaka Germ Cells Phenotype Gene Knockdown Techniques embryonic structures Molecular Medicine biological phenomena cell phenomena and immunity Chromatin immunoprecipitation Developmental Biology

description

Abstract 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.

year	journal	country	edition	language
2010-01-01	Stem Cells

https://doi.org/10.1002/stem.469