Species: mouse
Mutation name: None
type: null mutation
fertility: infertile - ovarian defect
Comment: GATA-like factor 1 (GLP-1) is required for normal germ cell development during embryonic oogenesis. Strauss TJ et al. Oogenesis and primordial follicle formation are tightly linked processes requiring organized and precisely timed communication between somatic and germ cells. Deviations in ovarian cell cross talk, or aberrant gene expression within one of the cell populations, can lead to follicle loss or dysfunction, resulting in infertility. Expression of GATA like protein-1 (Glp-1) in ovarian somatic cells is required for normal fertility in female mice, as Glp-1 deficiency leads to the absence of oocytes at birth. However, the timing and nature of this germ cell loss is not well understood. Here we characterize the embryonic germ cell loss in Glp-1 null mice. Quantitative PCR demonstrates that ovarian Glp-1 mRNA is expressed in a bimodal pattern during embryogenesis, peaking at E13.5-14.5 and again at birth. In contrast, adult ovaries express low but detectable levels of Glp-1 mRNA. Analysis of developing Glp-1 null mouse ovaries shows that germ cells are appropriately specified and migrate normally to nascent gonads. Upon arrival at the gonad, precocious loss of germ cells begins at around E13.5. This loss is completed by birth and is accompanied by defects in the expression of genes associated with meiotic entry. Interestingly, somatic pregranulosa cells still form basement membranes surrounding germ line cysts and express mRNA encoding paracrine signaling molecules that communicate with oocytes, albeit at lower levels than normal. Together, these data imply that the somatic cell protein Glp-1 is not necessary for many pregranulosa cell functions but is required for germ cell survival.

Species: mouse
Mutation name: None
type: null mutation
fertility: infertile - ovarian defect
Comment: GLP-1: a novel zinc finger protein required in somatic cells of the gonad for germ cell development. Li S et al. Mouse gonadal development is regulated by a variety of transcription factors. Here we report the identification and characterization of a novel nuclear zinc finger protein called GATA like protein-1 (GLP-1), which is expressed at high levels in the somatic cells of the developing gonads, including Leydig cells in the testes and granulosa cells in the ovaries. Biochemical analysis of GLP-1 shows that it acts as a transcriptional repressor of GATA factor function. To determine the necessity of GLP-1 in gonadal development, a null allele in mice was generated by replacing all of the coding exons with the bacterial lacZ gene. GLP-1(lacZ) null mice are viable with no detectable defects in visceral organ development; however, both males and females are completely infertile. Loss of GLP-1 leads to defective sperm development in males with a marked reduction in mature spermatids observed as early as postnatal week 1. In females, loss of GLP-1 leads to a severe block in germ cell development as early as E17.5. Together, these data identify GLP-1 as a critical nuclear repressor in somatic cells of the gonad that is required for germ cell development, and highlight the importance of somatic-germ cell interactions in the regulation of this critical process.

Species: mouse
Mutation name:
type: targeted overexpression
fertility: fertile
Comment: ZGLP1 is a determinant for the oogenic fate in mice. Nagaoka SI et al. (2020) Mammalian sexual reproduction relies on the dichotomy of male and female germ cell development. However, the underlying mechanisms remain unclear. Here, we show that ZGLP1, a conserved transcriptional regulator with GATA-like zinc fingers, determines the oogenic fate in mice. ZGLP1 acts downstream of bone morphogenetic protein (BMP), but not retinoic acid (RA), and is essential for the oogenic program and meiotic entry. ZGLP1 overexpression induces differentiation of in vitro primordial germ cell-like cells (PGCLCs) into fetal oocytes by activating the oogenic programs repressed by Polycomb activities, whereas RA signaling contributes to the oogenic program maturation and PGC program repression. Our findings elucidate the mechanism for mammalian oogenic fate determination, providing a foundation for promoting in vitro gametogenesis and reproductive medicine.//////////////////