Germline regulatory element of Oct-4 specific for the totipotent cycle of embryonal cells

TLDR

Oct‑4 is expressed in totipotent stem cells of the pregastrulation mouse embryo and is downregulated during gastrulation, remaining only in the germline lineage. Oct‑4/lacZ transgenes were employed to map the regulatory architecture, revealing two distinct elements that govern the spatial and temporal pattern of Oct‑4 expression. Two distinct regulatory elements were identified: a distal element that activates Oct‑4 in preimplantation embryos and primordial germ cells but not in epiblast cells, and a proximal element that drives epiblast‑specific expression and its gastrulation‑dependent downregulation, demonstrating that germline Oct‑4 expression is regulated separately from epiblast expression and providing a marker for totipotent cells.

Abstract

ABSTRACT The totipotential stem cells of the pregastrulation mouse embryo which give rise to all embryonic somatic tissues and germ cells express Oct-4. The expression is downregulated during gastrulation and is thereafter only maintained in the germline lineage. Oct-4/lacZ transgenes were used to determine how this pattern of expression was achieved, and resulted in the identification of two separate regulatory elements. The distal element drives Oct-4 expression in preimplantation embryos, in migratory and postmigratory primordial germ cells but is inactive in cells of the epiblast. In cell lines this element is specifically active in embryonic stem and embryonic germ cells. The proximal element directs the epiblast-specific expression pattern, including downregulation during gastrulation; in cell lines its activity is restricted to epiblast-derived cells. Thus, Oct-4 expression in the germline is regulated separately from epiblast expression. This provides the first marker for the identification of totipotent cells in the embryo, and suggests that expression of Oct-4 in the totipotent cycle is dependent on a set of factors unique to the germline.