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Early asymmetric cues triggering the dorsal/ventral gene regulatory network of the sea urchin embryo.

Cavalieri V, Spinelli G - Elife (2014)

Bottom Line: Remarkably, the localized knock-down of nodal restores DV polarity of embryos lacking hbox12 function.Finally, we show that hbox12 is a dorsal-specific negative modulator of the p38-MAPK activity, which is required for nodal expression.Altogether, our results suggest that Hbox12 function is essential for proper positioning of the DV organizer.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, Palermo, Italy.

ABSTRACT
Dorsal/ventral (DV) patterning of the sea urchin embryo relies on a ventrally-localized organizer expressing Nodal, a pivotal regulator of the DV gene regulatory network. However, the inceptive mechanisms imposing the symmetry-breaking are incompletely understood. In Paracentrotus lividus, the Hbox12 homeodomain-containing repressor is expressed by prospective dorsal cells, spatially facing and preceding the onset of nodal transcription. We report that Hbox12 misexpression provokes DV abnormalities, attenuating nodal and nodal-dependent transcription. Reciprocally, impairing hbox12 function disrupts DV polarity by allowing ectopic expression of nodal. Clonal loss-of-function, inflicted by blastomere transplantation or gene-transfer assays, highlights that DV polarization requires Hbox12 action in dorsal cells. Remarkably, the localized knock-down of nodal restores DV polarity of embryos lacking hbox12 function. Finally, we show that hbox12 is a dorsal-specific negative modulator of the p38-MAPK activity, which is required for nodal expression. Altogether, our results suggest that Hbox12 function is essential for proper positioning of the DV organizer.

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Model for establishment of the DV organizing centre in the sea urchin embryo.In the early embryo, hbox12 transcription is initiated by combinatorial positive inputs from Otx and probably Sox in the future dorsal ectoderm (Cavalieri et al., 2008). hbox12-dependent suppression of nodal gene expression in these cells is mediated by the transient inactivation of p38 and/or probably by direct repression. On the ventral side of the embryo, hbox12 expression is negatively regulated by unidentified repressors (Cavalieri et al., 2008). In these cells, active p38 stimulates nodal expression probably through Oct1/2 or other intermediate transcription factors (Range and Lepage, 2011), allowing the establishment of the DV organizer and patterning along the secondary axis.DOI:http://dx.doi.org/10.7554/eLife.04664.016
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fig9: Model for establishment of the DV organizing centre in the sea urchin embryo.In the early embryo, hbox12 transcription is initiated by combinatorial positive inputs from Otx and probably Sox in the future dorsal ectoderm (Cavalieri et al., 2008). hbox12-dependent suppression of nodal gene expression in these cells is mediated by the transient inactivation of p38 and/or probably by direct repression. On the ventral side of the embryo, hbox12 expression is negatively regulated by unidentified repressors (Cavalieri et al., 2008). In these cells, active p38 stimulates nodal expression probably through Oct1/2 or other intermediate transcription factors (Range and Lepage, 2011), allowing the establishment of the DV organizer and patterning along the secondary axis.DOI:http://dx.doi.org/10.7554/eLife.04664.016

Mentions: The events that drive the transcriptional regulation of nodal are not completely understood. An interesting line of questioning to pursue in the future would be to evaluate whether Hbox12 directly represses nodal transcription in dorsal cells. Intriguingly, several consensus binding sites for homeodomain-containing factors do exist within the promoter sequence of the nodal gene (Range et al., 2007). On this basis, we cannot exclude the direct association of Hbox12 to the cis-regulatory apparatus of nodal (Figure 9).10.7554/eLife.04664.016Figure 9.Model for establishment of the DV organizing centre in the sea urchin embryo.


Early asymmetric cues triggering the dorsal/ventral gene regulatory network of the sea urchin embryo.

Cavalieri V, Spinelli G - Elife (2014)

Model for establishment of the DV organizing centre in the sea urchin embryo.In the early embryo, hbox12 transcription is initiated by combinatorial positive inputs from Otx and probably Sox in the future dorsal ectoderm (Cavalieri et al., 2008). hbox12-dependent suppression of nodal gene expression in these cells is mediated by the transient inactivation of p38 and/or probably by direct repression. On the ventral side of the embryo, hbox12 expression is negatively regulated by unidentified repressors (Cavalieri et al., 2008). In these cells, active p38 stimulates nodal expression probably through Oct1/2 or other intermediate transcription factors (Range and Lepage, 2011), allowing the establishment of the DV organizer and patterning along the secondary axis.DOI:http://dx.doi.org/10.7554/eLife.04664.016
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4273433&req=5

fig9: Model for establishment of the DV organizing centre in the sea urchin embryo.In the early embryo, hbox12 transcription is initiated by combinatorial positive inputs from Otx and probably Sox in the future dorsal ectoderm (Cavalieri et al., 2008). hbox12-dependent suppression of nodal gene expression in these cells is mediated by the transient inactivation of p38 and/or probably by direct repression. On the ventral side of the embryo, hbox12 expression is negatively regulated by unidentified repressors (Cavalieri et al., 2008). In these cells, active p38 stimulates nodal expression probably through Oct1/2 or other intermediate transcription factors (Range and Lepage, 2011), allowing the establishment of the DV organizer and patterning along the secondary axis.DOI:http://dx.doi.org/10.7554/eLife.04664.016
Mentions: The events that drive the transcriptional regulation of nodal are not completely understood. An interesting line of questioning to pursue in the future would be to evaluate whether Hbox12 directly represses nodal transcription in dorsal cells. Intriguingly, several consensus binding sites for homeodomain-containing factors do exist within the promoter sequence of the nodal gene (Range et al., 2007). On this basis, we cannot exclude the direct association of Hbox12 to the cis-regulatory apparatus of nodal (Figure 9).10.7554/eLife.04664.016Figure 9.Model for establishment of the DV organizing centre in the sea urchin embryo.

Bottom Line: Remarkably, the localized knock-down of nodal restores DV polarity of embryos lacking hbox12 function.Finally, we show that hbox12 is a dorsal-specific negative modulator of the p38-MAPK activity, which is required for nodal expression.Altogether, our results suggest that Hbox12 function is essential for proper positioning of the DV organizer.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, Palermo, Italy.

ABSTRACT
Dorsal/ventral (DV) patterning of the sea urchin embryo relies on a ventrally-localized organizer expressing Nodal, a pivotal regulator of the DV gene regulatory network. However, the inceptive mechanisms imposing the symmetry-breaking are incompletely understood. In Paracentrotus lividus, the Hbox12 homeodomain-containing repressor is expressed by prospective dorsal cells, spatially facing and preceding the onset of nodal transcription. We report that Hbox12 misexpression provokes DV abnormalities, attenuating nodal and nodal-dependent transcription. Reciprocally, impairing hbox12 function disrupts DV polarity by allowing ectopic expression of nodal. Clonal loss-of-function, inflicted by blastomere transplantation or gene-transfer assays, highlights that DV polarization requires Hbox12 action in dorsal cells. Remarkably, the localized knock-down of nodal restores DV polarity of embryos lacking hbox12 function. Finally, we show that hbox12 is a dorsal-specific negative modulator of the p38-MAPK activity, which is required for nodal expression. Altogether, our results suggest that Hbox12 function is essential for proper positioning of the DV organizer.

Show MeSH
Related in: MedlinePlus