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Efficient retina formation requires suppression of both Activin and BMP signaling pathways in pluripotent cells.

Wong KA, Trembley M, Abd Wahab S, Viczian AS - Biol Open (2015)

Bottom Line: We determined the effect of these treatments on retina formation using the Animal Cap Transplant (ACT) assay; in which treated pluripotent cells were transplanted into the eye field of host embryos.We found that inhibition of Activin signaling, in the presence of BMP signaling inhibition, promotes efficient retinal specification in Xenopus tissue, mimicking the affect of adding Noggin alone.In whole embryos, we found that the eye field marker, rax, expanded when adding both dominant-negative Smad1 and Smad2, as did treating the cells with both dorsomorphin and SB431542.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY 13210, USA The Center for Vision Research, SUNY Eye Institute, Upstate Medical University, Syracuse, NY 13210, USA.

No MeSH data available.


Related in: MedlinePlus

Model of the intracellular pathways altered by Noggin to specify retinal progenitors.DM and SB43 inhibit activation of Smads by BMP and Activin receptors, respectively. In both pathways, gene transcription fails to drive epithelial or mesoderm specifying genes, which allows primitive ectoderm to take on a retinal progenitor cell fate.
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f08: Model of the intracellular pathways altered by Noggin to specify retinal progenitors.DM and SB43 inhibit activation of Smads by BMP and Activin receptors, respectively. In both pathways, gene transcription fails to drive epithelial or mesoderm specifying genes, which allows primitive ectoderm to take on a retinal progenitor cell fate.

Mentions: We have found that Noggin can direct pluripotent Xenopus animal caps to form fully functional retina (Viczian et al., 2009). Others have shown that Noggin overexpression alone is sufficient to generate retina in ventral blastomere cells normally, not fated to become retina (Moore and Moody, 1999). However, the molecular mechanism between Noggin treatment and retinal specification is still unknown. Our studies begin to address this question by investigating the signaling cascades downstream of Noggin to better understand how retina is specified. We present results in support of Noggin acting as both a BMP and Activin antagonist to regulate the specification of retinal progenitors (Fig. 8). We further investigated the role of each pathway by inhibiting their activity in pluripotent animal caps by expressing dominant-negative type II receptors tBRII and ΔXAR1, or by treating with the small molecule chemical inhibitors, dorsomorphin and SB431542. In each case, our results suggest that inhibition of BMP or Activin signaling alone led to mediocre retinal specification. However, when signaling through both pathways was inhibited, the treated cells expressed the EFTFs and generated retinal cells, as efficiently as Noggin. This suggests that at high concentrations Noggin induces retina by modulating both pathways. Cerberus, another BMP antagonist that is known to inhibit both BMP and Activin pathways, was able to specify retina as efficiently as Noggin. Follistatin, which is known to predominantly inhibit Activin signaling, was not as efficient. Collectively our results suggest that the dual inhibition of the BMP and Activin pathways directs pluripotent animal caps to generate retina as efficiently as Noggin.


Efficient retina formation requires suppression of both Activin and BMP signaling pathways in pluripotent cells.

Wong KA, Trembley M, Abd Wahab S, Viczian AS - Biol Open (2015)

Model of the intracellular pathways altered by Noggin to specify retinal progenitors.DM and SB43 inhibit activation of Smads by BMP and Activin receptors, respectively. In both pathways, gene transcription fails to drive epithelial or mesoderm specifying genes, which allows primitive ectoderm to take on a retinal progenitor cell fate.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4400599&req=5

f08: Model of the intracellular pathways altered by Noggin to specify retinal progenitors.DM and SB43 inhibit activation of Smads by BMP and Activin receptors, respectively. In both pathways, gene transcription fails to drive epithelial or mesoderm specifying genes, which allows primitive ectoderm to take on a retinal progenitor cell fate.
Mentions: We have found that Noggin can direct pluripotent Xenopus animal caps to form fully functional retina (Viczian et al., 2009). Others have shown that Noggin overexpression alone is sufficient to generate retina in ventral blastomere cells normally, not fated to become retina (Moore and Moody, 1999). However, the molecular mechanism between Noggin treatment and retinal specification is still unknown. Our studies begin to address this question by investigating the signaling cascades downstream of Noggin to better understand how retina is specified. We present results in support of Noggin acting as both a BMP and Activin antagonist to regulate the specification of retinal progenitors (Fig. 8). We further investigated the role of each pathway by inhibiting their activity in pluripotent animal caps by expressing dominant-negative type II receptors tBRII and ΔXAR1, or by treating with the small molecule chemical inhibitors, dorsomorphin and SB431542. In each case, our results suggest that inhibition of BMP or Activin signaling alone led to mediocre retinal specification. However, when signaling through both pathways was inhibited, the treated cells expressed the EFTFs and generated retinal cells, as efficiently as Noggin. This suggests that at high concentrations Noggin induces retina by modulating both pathways. Cerberus, another BMP antagonist that is known to inhibit both BMP and Activin pathways, was able to specify retina as efficiently as Noggin. Follistatin, which is known to predominantly inhibit Activin signaling, was not as efficient. Collectively our results suggest that the dual inhibition of the BMP and Activin pathways directs pluripotent animal caps to generate retina as efficiently as Noggin.

Bottom Line: We determined the effect of these treatments on retina formation using the Animal Cap Transplant (ACT) assay; in which treated pluripotent cells were transplanted into the eye field of host embryos.We found that inhibition of Activin signaling, in the presence of BMP signaling inhibition, promotes efficient retinal specification in Xenopus tissue, mimicking the affect of adding Noggin alone.In whole embryos, we found that the eye field marker, rax, expanded when adding both dominant-negative Smad1 and Smad2, as did treating the cells with both dorsomorphin and SB431542.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY 13210, USA The Center for Vision Research, SUNY Eye Institute, Upstate Medical University, Syracuse, NY 13210, USA.

No MeSH data available.


Related in: MedlinePlus