Gpbox (Psx2), a Homeobox Gene Preferentially Expressed in Female Germ Cells at the Onset of Sexual Dimorphism in Mice

Takasaki, N; McIsaac, R. Scott; Dean, Jurrien

doi:10.1006/dbio.2000.9741

Cited by 35 publications

(55 citation statements)

References 59 publications

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“…Genomic sequence data base searches with Ehox cDNA sequences has revealed a number of regions that are identical to sequences from the murine X chromosome, confirming this as the chromosomal location of Ehox. This is in keeping with the presence of other paired-like genes on this chromosome in the mouse (27).…”

Section: A Clone From An Es Cell Subtracted Library Encodes a Fragmensupporting

confidence: 84%

Cloning and Characterization of Ehox, a Novel Homeobox Gene Essential for Embryonic Stem Cell Differentiation

Jackson¹,

Baird²,

Cambray³

et al. 2002

Journal of Biological Chemistry

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We report here the identification and characterization of a novel paired-like homeobox-containing gene (Ehox). This gene, identified in embryonic stem (ES) cells, is differentially expressed during in vitro ES cell differentiation. We have assessed Ehox function using the ES cell in vitro differentiation system. This has involved molecular and biological analyses of the effects of sense or antisense Ehox expression (using episomal vectors) on ES cell differentiation. Analysis of antisense Ehox-expressing ES cells indicates that they are unable to express marker genes associated with hematopoietic, endothelial, or cardiac differentiation following removal of leukemia inhibitory factor. In contrast, overexpression of Ehox using the sense construct accelerated the appearance of these differentiation markers. ES cell self-renewal and differentiation assays reveal that inhibition of Ehox activity results in the maintenance of a stem cell phenotype in limiting concentrations of leukemia inhibitory factor and the almost complete impairment of the cardiomyocyte differentiation capacity of these cells. We therefore conclude that Ehox is a novel homeobox-containing gene that is essential for the earliest stages of murine ES cell differentiation. Murine embryonic stem (ES)1 cells are derived from the inner cell mass of the day 3.5 post coitus blastocyst and can be maintained in culture as a self-renewing totipotent population in the presence of the growth factor, leukemia inhibitory factor (LIF) (1, 2). These cells form the basis for much current murine transgenic and gene targeting technology (3) as they have the capacity to generate all tissues, including the germ line, when re-injected into the blastocyst (4, 5). ES cells can also differentiate in vitro into a wide range of cell types that are derived from all three embryological germ layers. These include hematopoietic lineages of mesodermal origin (6), neuronal cells of ectodermal origin (7), liver (8, 9) and pancreatic cell types derived from embryonic endoderm (10), as well as visceral and parietal extra-embryonic endoderm (11,12). With the isolation of human ES cells (13,14), it has been proposed that the in vitro differentiation capacity of these cells could be utilized for somatic cell therapy to treat a number of diseases (10,15,16). This technology, however, is severely limited by the heterogeneity of the differentiation process and by the limited molecular characterization of the system. A detailed analysis of the molecular mechanisms involved in the early differentiation steps may allow the development of lineage selection strategies (7) to generate therapeutic quantities of a specific cell type.One of the most closely studied differentiation pathways using the ES cell differentiation system has been the commitment to, and the differentiation of, hematopoietic stem cells (17-20). We have recently described the in vitro differentiation of ES cells, cultured as embryoid bodies (EBs), and the time course of commitment of these cells to the hemopoietic lineage (2...

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Section: A Clone From An Es Cell Subtracted Library Encodes a Fragmensupporting

confidence: 84%

Cloning and Characterization of Ehox, a Novel Homeobox Gene Essential for Embryonic Stem Cell Differentiation

Jackson¹,

Baird²,

Cambray³

et al. 2002

Journal of Biological Chemistry

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“…By contrast, Rhox9-null mice were not found to have any observable defects (Takasaki et al 2001). One explanation is that the functions of Rhox9 are compensated for by Rhox6, as these two genes are highly similar in sequence and expression pattern (Chun et al 1999, Takasaki et al 2000. But if Rhox6 does compensate for Rhox9, it does so without being upregulated, as Rhox6 mRNA is not increased in level in trophoblast cells, the testis, or ovary of Rhox9-null mice (Takasaki et al 2001).…”

Section: Expression and Functional Role Of Rhox Cluster Genesmentioning

confidence: 99%

“…The expression of Rhox genes in ES cells was determined by northern blot analysis (Sasaki et al 1991, Fan et al 1999, qPCR analysis (Jackson et al 2002, Fouse et al 2008, and semi-quantitative PCR analysis (Oda et al 2006). The expression of Rhox genes in the early embryo (blastocyst to E8.5) was determined by semiquantitative PCR analysis (Takasaki et al 2000, Jackson et al 2002, Chazaud et al 2006; while Rhox6 and Rhox9 cannot be detected in normal mouse embryos, they can be detected in Dnmt-mutant embryos deficient in DNA methylation by RT-PCR (33 cycles; Oda et al 2006). The expression of Rhox genes in fetal gonads was determined by qPCR and in situ hybridization analyses (Daggag et al 2008); these analyses demonstrated that all Rhox genes are predominantly expressed in primordial germ cells (PGCs), except for Rhox8, which was exclusively expressed in gonadal somatic cells (s).…”

Section: In Vivo Rhox5 Functionsmentioning

confidence: 99%

“…While it is not clear what selective forces are responsible for the recent amplification of these three genes in mice, it is clear that most of these paralogs are expressed and all but one (Rhox3d) encode full-length proteins and thus are presumably functional (Jackson et al 2006, Morris et al 2006, Wang & Zhang 2006. The b subcluster has five genes, including the founding Rhox family member -Rhox5 -and three other genes that had previously been given other names: Rhox6 (Psx1), Rhox8 (Tox), and Rhox9 (Psx2 and Gpbox) (Chun et al 1999, Takasaki et al 2000, Kang et al 2004. The g subcluster was originally defined as having three genes (MacLean et al 2005a), but recently, a fourth member has been identified: Rhox13 (Geyer & Eddy 2008).…”

Section: The Rhox Gene Clustermentioning

confidence: 99%

“…Their expression patterns suggest that Rhox genes may have both specific and broad roles regulating gametogenesis in both females and males. To date, the in vivo roles of only Rhox5 and Rhox9 (Pitman et al 1998, Takasaki et al 2000 have been reported (Fig. 2).…”

Section: Expression and Functional Role Of Rhox Cluster Genesmentioning

confidence: 99%

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The Rhox genes

MacLean¹,

Wilkinson²

2010

Reproduction

110

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Homeobox genes encode transcription factors that have crucial roles in embryogenesis. A recently discovered set of homeobox genes -the Rhox genes -are expressed during both embryogenesis and in adult reproductive tissues. The 33 known mouse Rhox genes are clustered together in a single region on the X chromosome, while likely descendents of the primodial Rhox cluster, Arx and Esx1, have moved to other positions on the X chromosome. Here, we summarize what is known about the regulation and function of Rhox cluster and Rhox-related genes during embryogenesis and gametogenesis. The founding member of the Rhox gene cluster -Rhox5 (previously known as Pem) -has been studied in the most depth and thus is the focus of this review. We also discuss the unusually rapid evolution of the Rhox gene cluster.

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Rhox homeobox gene cluster: recent duplication of three family members

MacLean

Lorenzetti

et al. 2006

genesis

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We recently reported the discovery of a homeobox gene cluster on the mouse X chromosome, Rhox, whose 12 members are selectively expressed in specific cell types in reproductive organs. Here we report the existence of 20 additional Rhox homeobox genes in this gene cluster. Most of the newly identified Rhox paralogs retain the same order and relative orientation as three of the originally described Rhox genes, suggesting that they arose from recent duplications of this trimer unit. Many of these new Rhox family members are expressed in the testis and placenta. Analysis of synonymous and nonsynonymous substitutions in their homeodomain region suggests that these new Rhox paralogs duplicated so recently that their encoded proteins have not yet acquired distinct DNA-binding specificities. The existence of these new Rhox genes provides an opportunity to examine the initial stages of gene cluster evolution.

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Gpbox (Psx2), a Homeobox Gene Preferentially Expressed in Female Germ Cells at the Onset of Sexual Dimorphism in Mice

Cited by 35 publications

References 59 publications

Cloning and Characterization of Ehox, a Novel Homeobox Gene Essential for Embryonic Stem Cell Differentiation

Cloning and Characterization of Ehox, a Novel Homeobox Gene Essential for Embryonic Stem Cell Differentiation

The Rhox genes

Rhox homeobox gene cluster: recent duplication of three family members

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