Zebrafish pou5f1/pou2, Homolog of Mammalian Oct4, Functions in the Endoderm Specification Cascade

Lunde, Karen; Belting, Heinz‐Georg; Driever, Wolfgang

doi:10.1016/j.cub.2003.11.022

Cited by 136 publications

(169 citation statements)

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“…Mosaic gene expression is a hallmark of embryonic development in notably mouse (Rossant and Tam, 2009) and zebrafish (Sprague et al, 2003;Lunde et al, 2004;Sprague et al, 2006) and may be at the origin of lineage specification. Whole-mount in situ hybridization of MBT + embryos showed that sox3 was ubiquitously expressed (Fig.…”

Section: Mosaic Klf4 Expression In Embryos Correlates With Co-detectimentioning

confidence: 99%

Chromatin states of developmentally-regulated genes revealed by DNA and histone methylation patterns in zebrafish embryos

Lindeman¹,

Winata²,

Aanes³

et al. 2010

Int. J. Dev. Biol.

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Embryo development proceeds from a cascade of gene activation and repression events controlled by epigenetic modifications of DNA and histones. Little is known about epigenetic states in the developing zebrafish, despite its importance as a model organism. We report here DNA methylation and histone modification profiles of promoters of developmentallyregulated genes (pou5f1, sox2, sox3, klf4, nnr, otx1b, nes, vasa), as well as tert and bactin2, in zebrafish embryos at the mid-late blastula transition, shortly after embryonic genome activation. We identify four classes of promoters based on the following profiles: (i) those enriched in marks of active genes (H3K9ac, H4ac, H3K4me3) without transcriptionally repressing H3K9me3 or H3K27me3; (ii) those enriched in H3K9ac, H4ac and H3K27me3, without H3K9me3; one such gene was klf4, shown by in situ hybridization to be mosaically expressed, likely accounting for the detection of both activating and repressive marks on its promoter; (iii) those enriched in H3K4me3 and H3K27me3 without acetylation; and (iv) those enriched in all histone modifications examined. Culture of embryo-derived cells under differentiation conditions leads to H3K9 and H4 deacetylation and H3K9 and H3K27 trimethylation on genes that are inactivated, yielding an epigenetic profile similar to those of fibroblasts or muscle. All promoters however retain H3K4me3, indicating an uncoupling of H3K4me3 occupancy and gene expression. All non-CpG island developmentallyregulated promoters are DNA unmethylated in embryos, but hypermethylated in fibroblasts. Our results suggest that differentially expressed embryonic genes are regulated by various patterns of histone modifications on unmethylated DNA, which create a developmentally permissive chromatin state.

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Section: Mosaic Klf4 Expression In Embryos Correlates With Co-detectimentioning

confidence: 99%

Chromatin states of developmentally-regulated genes revealed by DNA and histone methylation patterns in zebrafish embryos

Lindeman¹,

Winata²,

Aanes³

et al. 2010

Int. J. Dev. Biol.

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“…pou2 plays a zygotic role in the establishment of the midbrain-hindbrain organizer (Schier et al, 1996;Belting et al, 2001;Burgess et al, 2002;Reim and Brand, 2002). An earlier pou2 function for endoderm initiation was detected through analysis of maternal-zygotic (MZ) spg mutant embryos (Reim et al, 2004;Lunde et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Maternal control of vertebrate dorsoventral axis formation and epiboly by the POU domain protein Spg/Pou2/Oct4

2006

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Dorsoventral (DV) axis formation of the vertebrate embryo is controlled by the maternal genome and is subsequently refined zygotically. In the zygote, repression of ventralizing Bmp activity on the dorsal side through chordin and noggin is crucial for establishment of a dorsally located organizer. This interplay generates a zygotic Bmp activity gradient that defines distinct positional values along the DV axis. The maternal processes that control expression of the zygotic genes implicated in DV patterning are largely unknown. spiel-ohne-grenzen (spg/pou2) is a maternally and zygotically expressed zebrafish gene that encodes the POU domain transcription factor Pou2, an ortholog of mammalian Oct4/Pou5f1. We show that embryos that are genetically depleted of both maternal and zygotic pou2 function (MZspg) exhibit extreme DV patterning defects and, independently, a blastoderm-specific arrest of epiboly. Dorsal tissues expand to the ventral side at the expense of ventrolateral tissue in MZspg embryos. Dorsally expressed Bmp-antagonists, such as Chd and Nog1, and Gsc are ectopically activated at ventral levels in MZspg. Lack of ventral specification is apparent very early, suggesting that maternal processes are affected in MZspg. Indeed, maternal pou2 function is necessary to initiate zygotic expression of ventrally expressed genes such as bmp2b and bmp4, and for proper activation of bmp7, vox, vent and eve1. A constitutively active Alk8-TGF␤-receptor can ectopically induce bmp2b and bmp4 and rescues the dorsalization of MZspg. This indicates that pou2 acts upstream of Alk8, a maternally provided receptor implicated in the activation of zygotic bmp2b and bmp4 transcription. Consistent with this possibility, Bmp gene misexpression can rescue MZspg embryos, indicating that TGF␤-mediated signal transduction itself is intact in absence of Pou2. Inhibition of Fgf signaling, another pathway with early dorsalizing activity, can also restore and even ventralize MZspg embryos. The requirement for pou2 to initiate bmp2b expression can therefore be bypassed by releasing the repressive function of Fgf signaling upon bmp2b transcription. In transplantation experiments, we find that dorsalized cells from prospective ventrolateral regions of MZspg embryos are non cellautonomously respecified to a ventral fate within wild-type host embryos. Analysis of pou2 mRNA injected MZspg embryos shows that pou2 is required on the ventral side of cleavage stage embryos. Based on the maternal requirement for pou2 in ventral specification, we propose that ventral specification employs an active, pou2-dependent maternal induction step, rather than a default ventralizing program.

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“…Further, maternally contributed wild-type Crsp34 protein may partially rescue zygotic requirements for Crsp34 in mutant embryos during early phases of development. This constellation might mimic a specific function of Crsp34 in the formation of cell types that differentiate late in development, due to lower residual levels of maternal protein (compare to maternal rescue of zygotic functions for the Nodal coreceptor oep and pou5f1/spg genes described in Gritsman et al 1999 andLunde et al 2004). However, in crsp34 m885 mutant embryos a reduction of cells is observed in the ganglion and amacrine cell layers, whose progenitors lessen mutant siblings reveals a lower density in the central region of the mutant retina.…”

Section: Discussionmentioning

confidence: 99%

Differential Roles of Transcriptional Mediator Complex Subunits Crsp34/Med27, Crsp150/Med14 and Trap100/Med24 During Zebrafish Retinal Development

et al. 2006

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The transcriptional mediator complex has emerged as an important component of transcriptional regulation, yet it is largely unknown whether its subunits have differential functions in development. We demonstrate that the zebrafish mutation m885 disrupts a subunit of the mediator complex, Crsp34/ Med27. To explore the role of the mediator in the control of retinal differentiation, we employed two additional mutations disrupting the mediator subunits Trap100/Med24 and Crsp150/Med14. Our analysis shows that loss of Crsp34/Med27 decreases amacrine cell number, but increases the number of rod photoreceptor cells. In contrast, loss of Trap100/Med24 decreases rod photoreceptor cells. Loss of Crsp150/Med14, on the other hand, only slightly reduces dopaminergic amacrine cells, which are absent from both crsp34 m885 and trap100 lessen mutant embryos. Our data provide evidence for differential requirements for Crsp34/Med27 in developmental processes. In addition, our data point to divergent functions of the mediator subunits Crsp34/Med27, Trap100/Med24, and Crsp150/Med14 and, thus, suggest that subunit composition of the mediator contributes to the control of differentiation in the vertebrate CNS.

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Zebrafish pou5f1/pou2, Homolog of Mammalian Oct4, Functions in the Endoderm Specification Cascade

Cited by 136 publications

References 37 publications

Chromatin states of developmentally-regulated genes revealed by DNA and histone methylation patterns in zebrafish embryos

Chromatin states of developmentally-regulated genes revealed by DNA and histone methylation patterns in zebrafish embryos

Maternal control of vertebrate dorsoventral axis formation and epiboly by the POU domain protein Spg/Pou2/Oct4

Differential Roles of Transcriptional Mediator Complex Subunits Crsp34/Med27, Crsp150/Med14 and Trap100/Med24 During Zebrafish Retinal Development

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