Germ cell nuclear factor is not required for the down-regulation of pluripotency markers in fetal ovarian germ cells

Abstract

In mouse, germ cells retain expression of the pluripotency markers Oct4 and Nanog longer than any other cells in the body. While somatic cells repress these markers during gastrulation, female germ cells continue to express them until around the time of meiotic initiation. It is not yet clear why pluripotency markers are downregulated with this particular timing, nor is it understood what factors are involved in their repression. I have examined in fetal ovarian germ cells the expression and function of Gcnf (germ cell nuclear factor), an orphan nuclear receptor known to regulate both Oct4 and Nanog in gastrulating embryos. I have found that Gcnf is expressed in a female germ-cell-specific manner at the time when Oct4 and Nanog are down-regulated there. Gcnf mutants in which the ligand binding domain is disrupted display defects after gastrulation comparable to those observed in Gcnf-null mutants and those lacking the DNA binding domain. In contrast, the germ cells Gcnfligand binding domain mutants show no failure in repression of pluripotency markers, and other aspects of female germ cell development appear normal as well. Thus, it appears that the ligand binding domain of GCNF is not required for fetal ovarian germ cell development.